Prospects for combining immune checkpoint blockade with PARP inhibition

Li, Anping; Yi, Ming; Qin, Shuang; Chu, Qian; Luo, Suxia; Wu, Kongming

doi:10.1186/s13045-019-0784-8

Cited by 146Cancer Immunotherapy and BiomarkersPARP inhibition in cancer therapyImmunotherapy and Immune Responses

Prospects for combining immune checkpoint blockade with PARP inhibition

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Li, Anping, Yi, Ming, Qin, Shuang, Chu, Qian, Luo, Suxia, Wu, Kongming·2019·Journal of Hematology & Oncology

DOI 10.1186/s13045-019-0784-8PMC PMC6744711

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Abstract

The immunogenicity of a cancer cell is derived from accumulated somatic mutations. However, on the contrary to increased immunogenicity, anti-cancer immune response tends to be feeble. This impaired anti-cancer immunity could be attributed to multiple factors including loss of immunodominant epitopes, downregulation of major histocompatibility complex, and immunosuppressive microenvironment, as well as aberrant negative co-stimulatory signals. Immune checkpoint inhibitors block negative co-stimulatory signals such as programmed cell death-1 and cytotoxic T-lymphocyte-associated protein 4, ultimately reactivating anti-cancer immunity. Immune checkpoint inhibitors elicit potent anti-cancer effect and have been approved for multiple cancers. Nevertheless, there still are significant potential improvements for the applications of checkpoint inhibitor, especially considering frequent resistance. Recent studies demonstrated that additional PARP inhibition could alleviate resistance and enhance efficacy of immune checkpoint blockade therapy via promoting cross-presentation and modifying immune microenvironment. We proposed that PARP inhibitors could enhance the priming and tumor-killing activities of T cell, boost the whole cancer-immunity cycle, and thereby improve the response to immune checkpoint blockade. In this review, we focused the latest understanding of the effect of PARP inhibitors on anti-cancer immunity and PARP inhibitors combining immune checkpoint blockade therapy. Moreover, we summarized the preclinical and clinical evidence and discussed the feasibility of this combination therapy in future clinical practice.

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Some HR-deficient (e.g., BRCA1/2 mutant) cancer cells only repair DSB by nonhomologous end joining, a low-fidelity repair pathway.
“However, some HR-deficient (e.g. BRCA1/2 mutant) cancer cells only repair DSB by nonhomologous end joining, which is a low fidelity repair pathway [219].”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [219]
Normal cells preferentially repair double-strand breaks via homologous recombination.
“Normal cells preferentially repair double strand break (DSB) via homologous recombination (HR).”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [219]

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Ding, L., Kim, H.-J., Wang, Q., Kearns, M., Jiang, T., Ohlson, C. E., Li, B. B., Xie, S., Liu, J. F., Stover, E. H., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.11.054 · Cited by 572 · cited 10× · see citing works
“In the peripheral blood of mice undergoing Olaparib treatment, CD8+ T cells possessed greater capability to produce IFN-γ and TNFα [118].”
BackgroundInfluential
Proteomic Profiling Identifies Dysregulated Pathways in Small Cell Lung Cancer and Novel Therapeutic Targets Including PARP1
Byers, L. A., Wang, J., Nilsson, M. B., Fujimoto, J., Saintigny, P., Yordy, J. S., Giri, U. P., Peyton, M., Fan, Y. H., Diao, L., et al. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0112 · Cited by 553 · cited 1× · see citing works
“Dysregulated cell cycle checkpoint leads to increased replication stress [122].”
Background
Alterations in DNA damage response and repair genes as potential marker of clinical benefit from PD-1/PD-L1 blockade in advanced urothelial cancers
Teo, M. Y., Seier, K., Ostrovnaya, I., Regazzi, A. M., Kania, B. E., Moran, M. M., Cipolla, C. K., Bluth, M. J., Chaim, J., Al-Ahmadie, H., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2017.75.7740 · Cited by 544 · cited 1× · see citing works
“After receiving anti-PD-1/ PD-L1 treatment, patients with DDR deficiencies had a higher response rate compared with patients without these deficiencies [95].”
Background
Selective effects of PD-1 on Akt and Ras pathways regulate molecular components of the cell cycle and inhibit T cell proliferation
Patsoukis, N., Brown, J., Petkova, V., Liu, F., Li, L., & Boussiotis, V. A. (2012) · Science Signaling · doi:10.1126/scisignal.2002796 · Cited by 529 · cited 1× · see citing works
“Besides, PD-1/PD-L1 signal could also suppress intercellular PI3K-Akt and Ras-Raf-MAPK signaling pathways, which further downregulates glycolysis, the metabolism of amino acid and fatty acid oxidation, as well as cell proliferation [68, 69].”
Background
Loss of 53BP1 Causes PARP Inhibitor Resistance in Brca1 -Mutated Mouse Mammary Tumors
Jaspers, J. E., Kersbergen, A. J., Boon, U., Sol, W., van Deemter, L., Zander, S. A. L., Drost, R., Wientjens, E., Ji, J. J., Aly, A., et al. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0049 · Cited by 515 · see citing works
The diverse roles and clinical relevance of PARPs in DNA damage repair: Current state of the art
Vos, M. D., Schreiber, V., & Dantzer, F. (2012) · Biochemical Pharmacology · doi:10.1016/j.bcp.2012.03.018 · Cited by 491 · cited 1× · see citing works
“PARP is a core DNA damage sensor in DDR, which binds to damaged DNA lesions, catalyzes the generation of negatively charged poly (ADP-ribose) chains, remodels the structures of damaged chromatin, and recruits DNA repair-related protein complex [29, 30].”
Background
Mechanisms of resistance to therapies targeting BRCA-mutant cancers
Lord, C. J., & Ashworth, A. (2013) · Nature Medicine · doi:10.1038/nm.3369 · Cited by 456 · cited 1× · see citing works
“In spite of the great success of PARPi in a particular population, there are some problems needing to be properly resolved, especially acquired PARPi resistance [51].”
Background
Immunotherapy and targeted therapy combinations in metastatic breast cancer
Esteva, F. J., Hubbard-Lucey, V. M., Tang, J., & Pusztai, L. (2019) · The Lancet Oncology · doi:10.1016/s1470-2045(19)30026-9 · Cited by 452 · cited 1× · see citing works
“In the meanwhile, based on the hypothesis that patients with mutations in BRCA1/2 or other HR components are prone to possess higher mutation burden, multiple clinical trials are ongoing to explore the efficacy of combination therapy of PARPi and immune checkpoint inhibitors [56].”
Background
Activating cGAS-STING pathway for the optimal effect of cancer immunotherapy
Li, A., Yi, M., Qin, S., Song, Y., Chu, Q., & Wu, K. (2019) · Journal of Hematology & Oncology · doi:10.1186/s13045-019-0721-x · Cited by 413 · cited 1× · see citing works
“Therefore, immunotherapy-based combination strategy attracts extensive attention for synergistic efficacy and lower risk of resistance [20, 21].”
BackgroundSelf-citation
Pembrolizumab in patients with CLL and Richter transformation or with relapsed CLL
Ding, W., LaPlant, B. R., Call, T. G., Parikh, S. A., Leis, J. F., He, R. L., Shanafelt, T. D., Sinha, S., Le‐Rademacher, J. G., Feldman, A. L., et al. (2017) · Blood · doi:10.1182/blood-2017-02-765685 · Cited by 404 · cited 1× · see citing works
“The level of PD-L1 is a vital biomarker predicting the efficacy of anti-PD-1/PD-L1 efficacy [86, 113].”
Background
New development in CAR-T cell therapy
Wang, Z., Wu, Z., Liu, Y., & Han, W. (2017) · Journal of Hematology & Oncology · doi:10.1186/s13045-017-0423-1 · Cited by 395 · see citing works
A two-step, two-signal model for the primary activation of precursor helper T cells
Bretscher, P. A. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.1.185 · Cited by 386 · cited 2× · see citing works
“The first signal is the specific binding between T cell receptor (TCR) and antigenic peptide-major histocompatibility complex (pMHC) [59].”
Background
Immune activation and response to pembrolizumab in POLE-mutant endometrial cancer
Mehnert, J. M., Panda, A., Zhong, J., Hirshfield, K. M., Damare, S., Lane, K., Sokol, L. O., Stein, M. N., Rodriguez-Rodriquez, L., Kaufman, H. L., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci84940 · Cited by 373 · see citing works
Axitinib in combination with pembrolizumab in patients with advanced renal cell cancer: a non-randomised, open-label, dose-finding, and dose-expansion phase 1b trial
Atkins, M. B., Plimack, E. R., Puzanov, I. J., Fishman, M., McDermott, D. F., Cho, D. C., Vaishampayan, U. N., George, S., Olencki, T. E., Tarazi, J., et al. (2018) · The Lancet Oncology · doi:10.1016/s1470-2045(18)30081-0 · Cited by 370 · see citing works
Secondary mutations in BRCA2 associated with clinical resistance to a PARP inhibitor
Barber, L. J., Sandhu, S. K., Chen, L., Campbell, J., Kozarewa, I., Fenwick, K., Assiotis, I., Rodrigues, D. N., Reis-Filho, J. S., Moreno, V., et al. (2012) · The Journal of Pathology · doi:10.1002/path.4140 · Cited by 337 · see citing works
PARP Inhibitors: Extending Benefit Beyond BRCA -Mutant Cancers
Pilie, P. G., Gay, C. M., Byers, L. A., O’Connor, M. J., & Yap, T. A. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-0968 · Cited by 334 · cited 4× · see citing works
“The viability of SCLC is highly dependent on hyperactive PARP, thus SCLC is prone to be sensitive to PARPi treatment [92].”
BackgroundInfluential
PARP inhibition enhances tumor cell-intrinsic immunity in ERCC1-deficient non-small cell lung cancer
Chabanon, R. M., Muirhead, G., Krastev, D. B., Adam, J., Morel, D., Garrido, M., Lamb, A., Hénon, C., Dorvault, N., Rouanne, M., et al. (2019) · Journal of Clinical Investigation · doi:10.1172/jci123319 · Cited by 332 · cited 2× · see citing works
“PARPi-mediated catastrophic DNA damage and subsequently acute inflammation could rapidly elevate the abundance of type I IFN via cGASSTING pathway [117].”
Background
Structural Basis of Detection and Signaling of DNA Single-Strand Breaks by Human PARP-1
Eustermann, S., Wu, W.-F., Langelier, M.-F., Yang, J., Easton, L. E., Riccio, A. A., Pascal, J. M., & Neuhaus, D. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.10.032 · Cited by 320 · see citing works
Activity of durvalumab plus olaparib in metastatic castration-resistant prostate cancer in men with and without DNA damage repair mutations
Karzai, F. H., VanderWeele, D. J., Madan, R. A., Owens, H., Cordes, L. M., Hankin, A., Couvillon, A., Nichols, E. H., Bilušić, M., Beshiri, M. L., et al. (2018) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-018-0463-2 · Cited by 310 · see citing works
T cell anergy and costimulation
Appleman, L. J., & Boussiotis, V. A. (2003) · Immunological Reviews · doi:10.1034/j.1600-065x.2003.00009.x · Cited by 306 · cited 1× · see citing works
“Contrary to the first signal, the second signal is a non-antigen-specific pathway which depends on the binding between costimulatory molecules and corresponding ligands [60].”
Background
Chimeric antigen receptor T cells: a novel therapy for solid tumors
Yu, S., Li, A., Liu, Q., Li, T., Yuan, X., Han, X., & Wu, K. (2017) · Journal of Hematology & Oncology · doi:10.1186/s13045-017-0444-9 · Cited by 306 · see citing works
Self-citation
Combined Radiotherapy and Anti–PD-L1 Antibody Synergistically Enhances Antitumor Effect in Non–Small Cell Lung Cancer
Gong, X., Li, X., Jiang, T., Xie, H., Zhu, Z., Zhou, F., & Zhou, C. (2017) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2017.04.014 · Cited by 299 · see citing works
PD-1/PD-L1 Blockade: Have We Found the Key to Unleash the Antitumor Immune Response?
Xu-Monette, Z. Y., Zhang, M., Li, J., & Young, K. H. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01597 · Cited by 290 · cited 1× · see citing works
“However, the clinical application of ICIs is limited by low response rate [82].”
Background
CTLA-4 Blockade Synergizes Therapeutically with PARP Inhibition in BRCA1-Deficient Ovarian Cancer
Higuchi, T., Flies, D. B., Marjon, N. A., Mantia-Smaldone, G. M., Ronner, L., Gimotty, P. A., & Adams, S. F. (2015) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-15-0044 · Cited by 286 · cited 13× · see citing works
“Combination therapy exhibited more potent anticancer effect and elevated the abundance of TILs compared with monotherapies [24].”
BackgroundMethodInfluential
DNA Damage Response: Three Levels of DNA Repair Regulation
Sirbu, B. M., & Cortez, D. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a012724 · Cited by 272 · cited 1× · see citing works
“Genome intensity is challenged by continuous DNA damage events [25].”
Background
Expression of CCR-7, MIP-3β, and Th-1 chemokines in type I IFN-induced monocyte-derived dendritic cells: importance for the rapid acquisition of potent migratory and functional activities
Parlato, S., Santini, S. M., Lapenta, C., Pucchio, T. D., Logozzi, M., Spada, M., Giammarioli, A. M., Malorni, W., Fais, S., & Belardelli, F. (2001) · Blood · doi:10.1182/blood.v98.10.3022 · Cited by 259 · cited 6× · see citing works
“PD-1 is expressed on multiple activated immune cells including T cells, B cells, natural killer (NK) cells, and dendritic cells (DCs) [63].”
BackgroundInfluential
Niraparib activates interferon signaling and potentiates anti-PD-1 antibody efficacy in tumor models
Wang, Z., Sun, K., Xiao, Y., Feng, B., Mikule, K., Ma, X., Feng, N., Vellano, C. P., Federico, L., Marszalek, J. R., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-38534-6 · Cited by 253 · cited 2× · see citing works
“found the concurrent ICI treatment remarkably enhanced the efficacy of PARPi in multiple BRCA-proficient tumors [120].”
Background
An Update on Poly(ADP-ribose)polymerase-1 (PARP-1) Inhibitors: Opportunities and Challenges in Cancer Therapy
Wang, Y.-Q., Wang, P., Wang, Y.-T., Yang, G., Zhang, A., & Miao, Z. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b00055 · Cited by 248 · cited 2× · see citing works
“Firstly, the capability of PARPi to inhibit PARP catalytic activity is not closely correlated to its cellkilling ability in BRCA-mutated tumors [32].”
Background
Development of PARP and immune-checkpoint inhibitor combinations
Stewart, R. A., Pilié, P. G., & Yap, T. A. (2018) · Cancer Research · doi:10.1158/0008-5472.can-18-2652 · Cited by 239 · cited 2× · see citing works
“In the absence of PARPi, low-level DNA damages at baseline induce the chronic inflammation which promotes the initiation and development of cancers [23].”
Background
Atezolizumab plus cobimetinib and vemurafenib in BRAF-mutated melanoma patients
Sullivan, R. J., Hamid, O., Gonzalez, R. C., Infante, J. R., Patel, M. R., Hodi, F. S., Lewis, K. D., Tawbi, H. A., Hernandez, G., Wongchenko, M. J., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0474-7 · Cited by 239 · see citing works
Mycobacterium tuberculosis Triggers Host Type I IFN Signaling To Regulate IL-1β Production in Human Macrophages
Novikov, A., Cardone, M., Thompson, R. W., Shenderov, K., Kirschman, K. D., Mayer-Barber, K. D., Myers, T. G., Rabin, R. L., Trinchieri, G., Sher, A., et al. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100926 · Cited by 238 · see citing works
Preclinical and clinical development of neoantigen vaccines
Li, L., Goedegebuure, S. P., & Gillanders, W. E. (2017) · Annals of Oncology · doi:10.1093/annonc/mdx681 · Cited by 234 · see citing works
Role of BRCA Mutations in Cancer Treatment with Poly(ADP-ribose) Polymerase (PARP) Inhibitors
Faraoni, I., & Graziani, G. (2018) · Cancers · doi:10.3390/cancers10120487 · Cited by 232 · cited 1× · see citing works
“However, for some cancer cells with HR deficiency such as BRCA1/2 mutations, NHEJ pathway is utilized for DSB repair [37].”
Immune checkpoint inhibitors, alone or in combination with chemotherapy, as first-line treatment for advanced non-small cell lung cancer. A systematic review and network meta-analysis
Dafni, U. G., Tsourti, Z., Vervita, K., & Peters, S. (2019) · Lung Cancer · doi:10.1016/j.lungcan.2019.05.029 · Cited by 223 · see citing works
IFN‐γ‐mediated inhibition of lung cancer correlates with PD‐L1 expression and is regulated by PI3K‐AKT signaling
Gao, Y., Yang, J., Cai, Y., Fu, S., Zhang, N., Fu, X., & Li, L. (2018) · International Journal of Cancer · doi:10.1002/ijc.31357 · Cited by 217 · see citing works
PARP inhibitors in ovarian cancer
Franzese, E., Centonze, S., Diana, A., Carlino, F., Guerrera, L. P., Napoli, M. D., Vita, F. D., Pignata, S., Ciardiello, F., & Orditura, M. (2018) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2018.12.002 · Cited by 214 · see citing works
Chimeric antigen receptor T-cell therapies for multiple myeloma
Mikkilineni, L., & Kochenderfer, J. N. (2017) · Blood · doi:10.1182/blood-2017-06-793869 · Cited by 213 · see citing works
Cancer immunotherapy beyond immune checkpoint inhibitors
Marin-Acevedo, J. A., Soyano, A. E., Dholaria, B., Knutson, K. L., & Lou, Y. (2018) · Journal of Hematology & Oncology · doi:10.1186/s13045-017-0552-6 · Cited by 213 · cited 1× · see citing works
“Although host immunity could theoretically recognize tumor-derived materials and retard tumor growth, a subset of cancer cells escape from immune surveillance and develop into visible tumor lesions [7].”
Background
Role of the cGAS–STING pathway in cancer development and oncotherapeutic approaches
Khoo, L. T., & Chen, L. (2018) · The EMBO Reports · doi:10.15252/embr.201846935 · Cited by 204 · cited 1× · see citing works
“As a result, these DNA damages persist in a low level which might increase the possibility of the exposure of doublestrand DNA (dsDNA) in cytoplasm [97].”
Background
CTLA-4 and T cell activation
Oosterwegel, M. A., Greenwald, R. J., Mandelbrot, D. A., Lorsbach, R. B., & Sharpe, A. H. (1999) · Current Opinion in Immunology · doi:10.1016/s0952-7915(99)80047-8 · Cited by 203 · cited 1× · see citing works
“The balance between positive and negative costimulatory signals is crucial for the activation and tolerance of T cells [61, 62].”
Background
Combination therapy strategies for improving PD‐1 blockade efficacy: a new era in cancer immunotherapy
Chowdhury, P. S., Chamoto, K., & Honjo, T. (2017) · Journal of Internal Medicine · doi:10.1111/joim.12708 · Cited by 193 · cited 1× · see citing works
“impairing immunosuppressive components [90].”
Type I IFN Drives a Distinctive Dendritic Cell Maturation Phenotype That Allows Continued Class II MHC Synthesis and Antigen Processing
Simmons, D. P., Wearsch, P. A., Canaday, D. H., Meyerson, H. J., Liu, Y. C., Wang, Y., Boom, W. H., & Harding, C. V. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1101313 · Cited by 186 · cited 6× · see citing works
“PD-1 is expressed on multiple activated immune cells including T cells, B cells, natural killer (NK) cells, and dendritic cells (DCs) [63].”
BackgroundInfluential
Biochemical Signaling of PD-1 on T Cells and Its Functional Implications
Boussiotis, V. A., Chatterjee, P., & Li, L. (2014) · The Cancer Journal · doi:10.1097/ppo.0000000000000059 · Cited by 186 · cited 1× · see citing works
“In the context of TCR stimulation, the immunoreceptor tyrosine-based inhibitory motif (ITIM) and immunoreceptor tyrosine-based switch motif (ITSM) of PD-1 are phosphorylated which further recruit SHP1/2 and counteract TCR/CD3-CD28 mediated tyrosine phosphorylation [66, 67].”
Background
Durvalumab in Combination with Olaparib in Patients with Relapsed SCLC: Results from a Phase II Study
Thomas, A., Vilimas, R. J., Trindade, C. J., Erwin-Cohen, R. A., Roper, N., Xi, L., Krishnasamy, V. P., Levy, E. B., Mammen, A., Nichols, S., et al. (2019) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2019.04.026 · Cited by 185 · see citing works
A Genetic Screen Using the PiggyBac Transposon in Haploid Cells Identifies Parp1 as a Mediator of Olaparib Toxicity
Pettitt, S. J., Rehman, F. L., Bajrami, I., Brough, R., Wållberg, F., Kozarewa, I., Fenwick, K., Assiotis, I., Chen, L., Campbell, J., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0061520 · Cited by 173 · see citing works
Update on Tumor Neoantigens and Their Utility: Why It Is Good to Be Different
Lee, C., Yelensky, R., Jooss, K. U., & Chan, T. A.-T. (2018) · Trends in Immunology · doi:10.1016/j.it.2018.04.005 · Cited by 162 · see citing works
Phase II trial of veliparib in patients with previously treated BRCA-mutated pancreas ductal adenocarcinoma
Lowery, M. A., Kelsen, D. P., Capanu, M., Smith, S., Lee, J. W., Stadler, Z. K., Moore, M. J., Kindler, H. L., Golan, T., Segal, A., et al. (2017) · European Journal of Cancer · doi:10.1016/j.ejca.2017.11.004 · Cited by 156 · see citing works
Colorectal cancer vaccines: Tumor-associated antigens vs neoantigens
Wagner, S., Mullins, C. S., & Linnebacher, M. (2018) · World Journal of Gastroenterology · doi:10.3748/wjg.v24.i48.5418 · Cited by 144 · cited 1× · see citing works
“Neoantigens are proteins exclusively expressed on cancer cells due to mutationmediated sequence alterations [4, 5].”
Background
TOPACIO/Keynote-162 (NCT02657889): A phase 1/2 study of niraparib + pembrolizumab in patients (pts) with advanced triple-negative breast cancer or recurrent ovarian cancer (ROC)—Results from ROC cohort.
Konstantinopoulos, P. A., Waggoner, S. E., Vidal, G. A., Mita, M. M., Fleming, G. F., Holloway, R. W., Le, L. V., Sachdev, J. C., Chapman‐Davis, E., Colón‐Otero, G., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2018.36.15_suppl.106 · Cited by 143 · see citing works
Checkpoint inhibitors in hematological malignancies
Ok, C. Y., & Young, K. H. (2017) · Journal of Hematology & Oncology · doi:10.1186/s13045-017-0474-3 · Cited by 136 · see citing works
Cellular and molecular mechanisms in cancer immune escape: a comprehensive review
Bhatia, A., & Kumar, Y. (2013) · Expert Review of Clinical Immunology · doi:10.1586/1744666x.2014.865519 · Cited by 134 · cited 1× · see citing works
“A growing body of evidence indicated that loss of cancer-specific immunodominant epitopes and T cell repertoire, downregulation of antigen processing, and presentation machinery, as well as immunosuppressive microenvironment could lead to immune tolerance to tumor antigens [9, 10].”
Background
The role of neoantigen in immune checkpoint blockade therapy
Yi, M., Qin, S., Zhao, W., Yu, S., Chu, Q., & Wu, K. (2018) · Experimental Hematology and Oncology · doi:10.1186/s40164-018-0120-y · Cited by 133 · see citing works
Self-citation
An open-label, phase II basket study of olaparib and durvalumab (MEDIOLA): Results in germline BRCA -mutated ( gBRCA m) platinum-sensitive relapsed (PSR) ovarian cancer (OC)
Drew, Y., de Jonge, M., Hong, S. H., Park, Y. H., Wolfer, A., Brown, J., Ferguson, M., Gore, M. E., Alvarez, R. H., Gresty, C., et al. (2018) · Gynecologic Oncology · doi:10.1016/j.ygyno.2018.04.555 · Cited by 131 · see citing works
Biochemical mechanisms of chromosomal translocations resulting from DNA double-strand breaks
Povirk, L. F. (2006) · DNA repair · doi:10.1016/j.dnarep.2006.05.016 · Cited by 131 · see citing works
A Phase II Study of Talazoparib after Platinum or Cytotoxic Nonplatinum Regimens in Patients with Advanced Breast Cancer and Germline BRCA1/2 Mutations (ABRAZO)
Turner, N. C., Telli, M. L., Rugo, H. S., Mailliez, A., Ettl, J., Grischke, E., Mina, L. A., Balmañà, J., Fasching, P. A., Hurvitz, S. A., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-1891 · Cited by 128 · see citing works
DNA double-strand break repair and chromosome translocations
Agarwal, S., Tafel, A. A., & Kanaar, R. (2006) · DNA repair · doi:10.1016/j.dnarep.2006.05.029 · Cited by 115 · cited 1× · see citing works
“HR is an effective repair approach with high fidelity which uses the sister copy of damaged sites as the template [36].”
Background
PD-1/PD-L blockade in gastrointestinal cancers: lessons learned and the road toward precision immunotherapy
Long, J., Lin, J., Wang, A., Wu, L., Zheng, Y., Yang, X., Wan, X., Xu, H., Chen, S., & Zhao, H. (2017) · Journal of Hematology & Oncology · doi:10.1186/s13045-017-0511-2 · Cited by 114 · cited 1× · see citing works
“A growing body of evidence indicated that loss of cancer-specific immunodominant epitopes and T cell repertoire, downregulation of antigen processing, and presentation machinery, as well as immunosuppressive microenvironment could lead to immune tolerance to tumor antigens [9, 10].”
Background
Interferon-α Suppresses cAMP to Disarm Human Regulatory T Cells
Bacher, N., Raker, V., Hofmann, C., Graulich, E., Schwenk, M., Baumgrass, R., Bopp, T., Zechner, U., Merten, L., Becker, C., et al. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-3788 · Cited by 103 · see citing works
PARP1 changes from three-dimensional DNA damage searching to one-dimensional diffusion after auto-PARylation or in the presence of APE1
Liu, L., Kong, M., Gassman, N. R., Freudenthal, B., Prasad, R., Zhen, S., Watkins, S. C., Wilson, S. H., & Houten, B. V. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx1047 · Cited by 93 · cited 1× · see citing works
“Then, PARP is dissociated from the DNA damage site by autoPARylation [31].”
Background
The promise of PD-1 inhibitors in gastro-esophageal cancers: microsatellite instability vs. PD-L1
Jin, Z., & Yoon, H. H. (2016) · Journal of Gastrointestinal Oncology · doi:10.21037/jgo.2016.08.06 · Cited by 89 · see citing works
Clinical applications of PD-L1 bioassays for cancer immunotherapy
Liu, D., Wang, S., & Bindeman, W. E. (2017) · Journal of Hematology & Oncology · doi:10.1186/s13045-017-0479-y · Cited by 86 · cited 1× · see citing works
“heterogeneity and dynamically evolving cancer antigen spectrum, it is hard to cure a tumor by monotherapy and tumors cells eventually acquire resistance [19].”
Background
Differential Toxicity in Patients with and without DNA Repair Mutations: Phase I Study of Carboplatin and Talazoparib in Advanced Solid Tumors
Dhawan, M. S., Bartelink, I. H., Aggarwal, R. R., Leng, J. X., Zhang, J. Z., Pawłowska, N., Terranova-Barberio, M., Grabowsky, J. A., Gewitz, A. D., Chien, A. J., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-0703 · Cited by 78 · cited 1× · see citing works
“It is notable that PARPi combining chemotherapy is easy to induce dose-limiting toxicity [55].”
Background
TOPACIO/Keynote-162: Niraparib + pembrolizumab in patients (pts) with metastatic triple-negative breast cancer (TNBC), a phase 2 trial.
Vinayak, S., Tolaney, S. M., Schwartzberg, L. S., Mita, M. M., McCann, G. A.-L., Tan, A. R., Wahner Hendrickson, A. E., Forero-Torres, A., Anders, C. K., Wulf, G. M., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2018.36.15_suppl.1011 · Cited by 77 · see citing works
Immune checkpoint inhibitors: new strategies to checkmate cancer
Wilson, R., Evans, T. R. J., Fraser, A. R., & Nibbs, R. J. B. (2017) · Clinical & Experimental Immunology · doi:10.1111/cei.13081 · Cited by 70 · cited 1× · see citing works
“CTLA-4 is constitutively expressed on Tregs and transiently upregulated on conventional T cells after activation [71].”
Background
Emerging therapies for breast cancer
Hu, X., Huang, W., & Fan, M. (2017) · Journal of Hematology & Oncology · doi:10.1186/s13045-017-0466-3 · Cited by 67 · see citing works
Poly(ADP-ribose) polymerase activity and inhibition in cancer
Dulaney, C. R., Marcrom, S., Stanley, J. A., & Yang, E. S.-H. (2017) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2017.01.007 · Cited by 64 · see citing works
New combinatorial strategies to improve the PARP inhibitors efficacy in the urothelial bladder Cancer treatment
Criscuolo, D., Morra, F., Giannella, R., Visconti, R., Cerrato, A., & Celetti, A. (2019) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-019-1089-z · Cited by 64 · cited 1× · see citing works
“The investigations of combination therapy were mainly conducted in BRCA1/2 mutated tumors [119].”
Background
A phase 2 study of olaparib and durvalumab in metastatic castrate-resistant prostate cancer (mCRPC) in an unselected population.
Karzai, F., Madan, R. A., Owens, H., Couvillon, A., Hankin, A., Williams, M., Bilusic, M., Cordes, L. M., Trepel, J. B., Killian, K., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2018.36.6_suppl.163 · Cited by 50 · cited 1× · see citing works
“The preliminary data of NCT02484404 showed that the combination therapy of Olaparib and Durvalumab effectively reduced tumor burden (measured by PSA reduction > 50%) in 8/17 unselected metastatic castrate-resistant prostate cancer [123].”
Background
Inhibition of homologous recombination by hyperthermia shunts early double strand break repair to non-homologous end-joining
Bergs, J. W. J., Krawczyk, P. M., Borovski, T., ten Cate, R., Rodermond, H. M., Stap, J., Medema, J. P., HAVEMAN, J., Essers, J., Chris van, B. R. E. E., et al. (2012) · DNA repair · doi:10.1016/j.dnarep.2012.10.008 · Cited by 49 · cited 10× · see citing works
“In normal cells, when both HR and NHEJ pathways are available in G2/M stage, HR pathway is preferentially adopted to repair DSB [35].”
BackgroundInfluential
The expression of cytotoxic mediators is altered in mononuclear cells of patients with melanoma and increased by interferon-alpha treatment
Guillot, B., Portalès, P., Du-Thanh, A., Merlet, S., Dereure, O., Clot, J., & Corbeau, P. (2005) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2005.06512.x · Cited by 48 · cited 1× · see citing works
“Thirdly, type I IFN could boost the function of cytotoxic T lymphocytes (CTLs) by increasing the generation of perforin 1 and granzyme B [106].”
Background
Cancer vaccine strategies: translation from mice to human clinical trials
Berzofsky, J. A., Terabe, M., Trepel, J. B., Pastan, I. H., Stroncek, D. F., Morris, J. C., & Wood, L. V. (2017) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-017-2084-x · Cited by 44 · see citing works
Immunotherapy in genitourinary malignancies
Mehta, K. D., Patel, K., & Parikh, R. A. (2017) · Journal of Hematology & Oncology · doi:10.1186/s13045-017-0457-4 · Cited by 42 · cited 1× · see citing works
“Since the first ICI was approved for metastatic melanoma patients in 2011, numerous ICIs have entered clinical practice [75, 76].”
Background
A Transendocytosis Perspective on the CD28/CTLA-4 Pathway
Soskic, B., Qureshi, O. S., Hou, T., & Sansom, D. M. (2014) · Advances in immunology · doi:10.1016/b978-0-12-800147-9.00004-2 · Cited by 41 · cited 1× · see citing works
“Subsequent internalization of CD80/CD86-CTLA-4 complex decreases the abundance of available co-stimulatory molecule ligands and elevates the threshold of T cell activation [73].”
Background
Dissecting PARP inhibitor resistance with functional genomics
Pettitt, S. J., & Lord, C. J. (2019) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2019.03.001 · Cited by 31 · cited 1× · see citing works
“The anti-cancer effect of PARPi has not been completely understood yet, which is initially attributed to inhibition of catalytic effect [33].”
Background
Unexpected Synergy Reveals New Therapeutic Strategy in SCLC
Drapkin, B. J., & Farago, A. F. (2019) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2019.03.005 · Cited by 24 · cited 1× · see citing works
“The preexisting TIL is the prerequisite of tumor-killing effect of ICI, thus PARPi could synergize with ICI and decrease the risk of drug resistance [112].”
Background

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Sorted by citations

Combination strategies with PD-1/PD-L1 blockade: current advances and future directions
Yi, M., Zheng, X., Niu, M., Zhu, S., Ge, H., & Wu, K. (2022) · Molecular Cancer · doi:10.1186/s12943-021-01489-2 · Cited by 1,445 · see citing works
“Inspired by the results of preclinical studies, numerous clinical studies are ongoing to evaluate the efficacy of PARPi combined with α-PD-1/PD-L1 [219].”
BackgroundSelf-citation
Understanding and overcoming resistance to PARP inhibitors in cancer therapy
Dias, M. P., Moser, S. C., Ganesan, S., & Jonkers, J. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00532-x · Cited by 526 · see citing works
Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial
Westin, S. N., Moore, K. N., Chon, H. S., Lee, J., Pepin, J. T., Sundborg, M., Shai, A., de la Garza, J., Nishio, S., Gold, M. A., et al. (2023) · Journal of Clinical Oncology · doi:10.1200/jco.23.02132 · Cited by 389 · see citing works
Tumor Immune Microenvironment during Epithelial–Mesenchymal Transition
Taki, M., Abiko, K., Ukita, M., Murakami, R., Yamanoi, K., Yamaguchi, K. D., Hamanishi, J., Baba, T., Matsumura, N., & Mandai, M. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-4459 · Cited by 357 · see citing works
“The FDA has approved several monoclonal antibodies targeting PD-1 (pembrolizumab, nivolumab, and cemiplimab) and PD-L1 (atezolizumab, avelumab, and durvalumab), which have been used as monotherapy or in combination with chemotherapies or other ICIs in several cancer types (27).”
BackgroundInfluential
Overcoming immunotherapy resistance in non-small cell lung cancer (NSCLC) - novel approaches and future outlook
Horvath, L., Thienpont, B., Zhao, L., Wolf, D. G. F., & Pircher, A. (2020) · Molecular Cancer · doi:10.1186/s12943-020-01260-z · Cited by 286 · see citing works
“As observed preclinically, PARPi induces genetic instability, increases TMB and neoantigen burden via DDR deficiency and may be involved in PD-L1 upregulation by cancer cells [97, 98].”
Background
The construction, expression, and enhanced anti-tumor activity of YM101: a bispecific antibody simultaneously targeting TGF-β and PD-L1
Yi, M., Zhang, J., Li, A., Niu, M., Yan, Y., Jiao, Y., Luo, S., Zhou, P., & Wu, K. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01045-x · Cited by 233 · see citing works
Self-citation
Advances in synthetic lethality for cancer therapy: cellular mechanism and clinical translation
Topatana, W., Juengpanich, S., Li, S., Cao, J., Hu, J., Lee, J., Suliyanto, K., Ma, D., Zhang, B., Chen, M., et al. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00956-5 · Cited by 182 · see citing works
Recent progress of metal‐based nanomaterials with anti‐tumor biological effects for enhanced cancer therapy
Lei, H.-L., Pei, Z.-F., Jiang, C., & Cheng, L. (2023) · Exploration · doi:10.1002/exp.20220001 · Cited by 105 · see citing works
Combine and conquer: manganese synergizing anti-TGF-β/PD-L1 bispecific antibody YM101 to overcome immunotherapy resistance in non-inflamed cancers
Yi, M., Niu, M., Zhang, J., Li, S., Zhu, S., Yan, Y., Li, N., Zhou, P., Chu, Q., & Wu, K. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01155-6 · Cited by 163 · see citing works
Self-citation
Applying artificial intelligence for cancer immunotherapy
Xu, Z., Wang, X., Zeng, S., Ren, X., Yan, Y., & Gong, Z. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.02.007 · Cited by 131 · see citing works
Recent developments in immunotherapy for gastrointestinal tract cancers
Chong, X., Madeti, Y., Cai, J., Li, W., Cong, L., Lu, J., Mo, L., Liu, H., He, S., Yu, C., et al. (2024) · Journal of Hematology & Oncology · doi:10.1186/s13045-024-01578-x · Cited by 129 · see citing works
Phase II study of ceralasertib (AZD6738) in combination with durvalumab in patients with advanced/metastatic melanoma who have failed prior anti-PD-1 therapy
Kim, R., Kwon, M., An, M., Kim, S. T., Smith, S. A., Loembé, A., Mortimer, P. G. S., Armenia, J., Lukashchuk, N., Shah, N., et al. (2021) · Annals of Oncology · doi:10.1016/j.annonc.2021.10.009 · Cited by 122 · see citing works
DNA Damage Response and Oxidative Stress in Systemic Autoimmunity
Souliotis, V. L., Vlachogiannis, N. I., Pappa, M. B., Argyriou, A., Ntouros, P. A., & Sfikakis, P. P. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms21010055 · Cited by 120 · see citing works
“Because targeting the DDR/R network can have an impact not only on cancer cells but also on host immunity, manipulation of molecular components of this network, alone or in combination with immune checkpoint inhibitors, has gained significant attention in cancer immunotherapy [148,149].”
Background
Avelumab Plus Talazoparib in Patients With Advanced Solid Tumors
Yap, T. A., Bardia, A., Dvorkin, M., Galsky, M. D., Beck, J. T., Wise, D. R., Karyakin, O. B., Rubovszky, G., Kislov, N. V., Rohrberg, K. S., et al. (2022) · JAMA Oncology · doi:10.1001/jamaoncol.2022.5228 · Cited by 110 · see citing works
Immune Checkpoint Inhibitors in Epithelial Ovarian Cancer: An Overview on Efficacy and Future Perspectives
Borella, F., Ghisoni, E., Giannone, G., Cosma, S. D., Benedetto, C., Valabrega, G., & Katsaros, D. (2020) · Diagnostics · doi:10.3390/diagnostics10030146 · Cited by 94 · see citing works
“In fact, PARPi interferes with homologous DNA damage repair, increases the mutational load in tumor cells and, in mouse models with mutations in BRCA genes, activates interferon-mediated pathways by acting in synergy with the inhibitors of immune checkpoint inhibitors [61].”
Background
Phase II study of ceralasertib (AZD6738) in combination with durvalumab in patients with advanced gastric cancer
Kwon, M., Kim, G., Kim, R., Kim, K., Kim, S. T., Smith, S. A., Mortimer, P. G. S., Hong, J. Y., Loembé, A., Irurzun‐Arana, I., et al. (2022) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2022-005041 · Cited by 93 · see citing works
Combination Strategies to Augment Immune Check Point Inhibitors Efficacy - Implications for Translational Research
Varayathu, H., Sarathy, V., Thomas, B. E., Mufti, S. S., & Naik, R. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.559161 · Cited by 94 · see citing works
“As discussed the immunological effects of PARP inhibitors are multifaceted (73), which includes”
Background
Therapeutic Targeting of DNA Damage Response in Cancer
Choi, W., & Lee, E. S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031701 · Cited by 91 · see citing works
“combination strategies are undergoing clinical investigation in a wide array of disease statuses [167].”
Background
PARP Inhibitors Resistance: Mechanisms and Perspectives
Giudice, E., Gentile, M., Salutari, V., Ricci, C., Musacchio, L., Carbone, M. V., Ghizzoni, V., Camarda, F., Tronconi, F., Nero, C., et al. (2022) · Cancers · doi:10.3390/cancers14061420 · Cited by 87 · see citing works
“Ongoing clinical trials are evaluating the clinical impact of this combination therapy [67].”
Background
The role of DNA damage repair (DDR) system in response to immune checkpoint inhibitor (ICI) therapy
Shi, C., Qin, K., Lin, A., Jiang, A., Cheng, Q., Liu, Z., Zhang, J., & Luo, P. (2022) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-022-02469-0 · Cited by 85 · see citing works
“It is generally understood that PARPi functions by blocking the BER pathway, or other repair factors, through its inhibition of the core DNA damage sensors and signal transducers, PARP1/2 enzymes [84, 116].”
BackgroundInfluential
Immunotherapy and Immunotherapy Combinations in Metastatic Castration-Resistant Prostate Cancer
Bansal, D., Reimers, M. A., Knoche, E. M., & Pachynski, R. K. (2021) · Cancers · doi:10.3390/cancers13020334 · Cited by 79 · see citing works
“PARP inhibition could potentiate immune modulation elicited by CPI by enhanced immune priming and T cell infiltration [185].”
Background
JASPER: Phase 2 trial of first‐line niraparib plus pembrolizumab in patients with advanced non–small cell lung cancer
Ramalingam, S. S., Thara, E., Awad, M. M., Dowlati, A., Haque, B., Stinchcombe, T. E., Dy, G. K., Spigel, D. R., Lu, S., Iyer Singh, N., et al. (2022) · Cancer · doi:10.1002/cncr.33885 · Cited by 75 · see citing works
The role of poly(ADP-ribose) polymerase inhibitors in the treatment of cancer and methods to overcome resistance: a review
Patel, M. A., Nowsheen, S., Maraboyina, S., & Xia, F. (2020) · Cell & Bioscience · doi:10.1186/s13578-020-00390-7 · Cited by 76 · see citing works
The Landscape of Novel Therapeutics and Challenges in Glioblastoma Multiforme: Contemporary State and Future Directions
Khaddour, K., Johanns, T. M., & Ansstas, G. (2020) · Pharmaceuticals · doi:10.3390/ph13110389 · Cited by 76 · see citing works
“Preclinical studies suggest that PARP inhibition with drugs such as olaparib can increase neoantigen formation, lead to PD-L1 upregulation, boost type I Interferon signaling, and reprogram TME to facilitate anti-tumor response when using ICI [179].”
Background
Targeting tumor-associated macrophages for successful immunotherapy of ovarian carcinoma
Truxová, I., Cibula, D., Špíšek, R., & Fucikova, J. P. (2023) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2022-005968 · Cited by 75 · see citing works
The Synergistic Effect of PARP Inhibitors and Immune Checkpoint Inhibitors
Wu, Z., Cui, P., Tao, H., Zhang, S., Ma, J., Liu, Z., Wang, J., Qian, Y., Chen, S., Huang, Z., et al. (2021) · Clinical Medicine Insights Oncology · doi:10.1177/1179554921996288 · Cited by 71 · see citing works
Role of DNA repair defects in predicting immunotherapy response
Zhang, J., Shih, D. J. H., & Lin, S. (2020) · Biomarker Research · doi:10.1186/s40364-020-00202-7 · Cited by 69 · see citing works
The developing landscape of combinatorial therapies of immune checkpoint blockade with DNA damage repair inhibitors for the treatment of breast and ovarian cancers
Zhu, L., Liu, J., Chen, J., & Zhou, Q. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01218-8 · Cited by 69 · see citing works
“Despite the weaker impact of homologous recombination (HR) deficiency on TMB relative to MMRd, catastrophic DNA damage driven by DDRi can be favorable to enhance ICB therapy efficiency [49].”
Background
Zinc finger proteins: guardians of genome stability
Kamaliyan, Z., & Clarke, T. L. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1448789 · Cited by 67 · see citing works
“Moreover, initial clinical trials of PARPi and anti-PDL-1 antibody combination has shown improved response rates compared to monotherapies in breast and ovarian cancer patients (Li et al., 2019).”
Background
Immunomodulatory Roles of PARP-1 and PARP-2: Impact on PARP-Centered Cancer Therapies
Yélamos, J., Moreno-Lama, L., Jimeno, J., & Ali, S. O. (2020) · Cancers · doi:10.3390/cancers12020392 · Cited by 69 · see citing works
N6-methyladenosine RNA modification in cancer therapeutic resistance: Current status and perspectives
Xu, Z., Peng, B., Cai, Y., Wu, G., Huang, J., Gao, M., Guo, G., Zeng, S., Gong, Z., & Yan, Y. (2020) · Biochemical Pharmacology · doi:10.1016/j.bcp.2020.114258 · Cited by 63 · see citing works
Pan-Cancer Analysis of PARP1 Alterations as Biomarkers in the Prediction of Immunotherapeutic Effects and the Association of Its Expression Levels and Immunotherapy Signatures
Zhang, X., Wang, Y., A, G., Qu, C., & Chen, J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.721030 · Cited by 76 · see citing works
“Current research found PARP1 inhibitors (PARPi) remodels tumor immune microenvironment, upregulates PDL1 and drives a systemic Th1-skewing immune response, which activates the priming of immunity and tumor-killing activity, in combination with ICIs for the renaissance of anti-tumor immunity (30), which is somewhat agr…”
Result
Endometrial Carcinoma: Immune Microenvironment and Emerging Treatments in Immuno-Oncology
Rousset-Rouviere, S., Rochigneux, P., Chrétien, A.-S., Fattori, S., Gorvel, L., Provansal, M., Lambaudie, É., Olive, D., & Sabatier, R. (2021) · Biomedicines · doi:10.3390/biomedicines9060632 · Cited by 60 · see citing works
“These drugs are thought to be able to enhance ICI activity via various pathways [75].”
Background
Synthetic Lethality through the Lens of Medicinal Chemistry
Myers, S. H., Ortega, J. A., & Cavalli, A. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00766 · Cited by 60 · see citing works
Advances of Targeted Therapy for Hepatocellular Carcinoma
Niu, M., Yi, M., Li, N., Wu, K., & Wu, K. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.719896 · Cited by 57 · see citing works
Self-citation
PARP Inhibitors in Breast and Ovarian Cancer
Wang, S. S. Y., Jie, Y. E., Cheng, S. W., Ling, G. L., & Heong, V. Y. M. (2023) · Cancers · doi:10.3390/cancers15082357 · Cited by 55 · see citing works
“Treatment with PARPi synergises with immune checkpoint inhibitors to enhance immune surveillance in the body by promoting cross-presentation, modifying immune microenvironments and increasing PD-L1 expression [77,78].”
Background
Molecular characteristics of BRCA1/2 and PALB2 mutations in pancreatic ductal adenocarcinoma
Seeber, A., Zimmer, K., Kocher, F., Puccini, A., Xiu, J., Nabhan, C., Elliott, A., Goldberg, R. M., Grothey, A. F., Shields, A. F., et al. (2020) · ESMO Open · doi:10.1136/esmoopen-2020-000942 · Cited by 52 · see citing works
“The hypothesis generated in this study should be evaluated further and must be proven in investigational trials.”
Precision medicine phase II study evaluating the efficacy of a double immunotherapy by durvalumab and tremelimumab combined with olaparib in patients with solid cancers and carriers of homologous recombination repair genes mutation in response or stable after olaparib treatment
Fumet, J.-D., Limagne, E., Thibaudin, M., Truntzer, C., Bertaut, A., Rederstorff, E., & Ghiringhelli, F. (2020) · BMC Cancer · doi:10.1186/s12885-020-07253-x · Cited by 48 · see citing works
“PARPi-mediated catastrophic DNA damage induces accumulated chromosome rearrangements, generates neoantigens and thus increases mutation burden [9].”
Background
Immune-Checkpoint Inhibitors in Platinum-Resistant Ovarian Cancer
Indini, A., Nigro, O., Lengyel, C. G., Ghidini, M., Petrillo, A., Lopez, S., Raspagliesi, F., Trapani, D., Khakoo, S. S., & Bogani, G. (2021) · Cancers · doi:10.3390/cancers13071663 · Cited by 46 · see citing works
“Available data on the prognostic and predictive significance of PD-1 and PD-L1 expression, as well as the presence of TILs, in OC, are inconsistent.”
BackgroundInfluential
In silico modeling and molecular docking insights of kaempferitrin for colon cancer-related molecular targets
Govindarasu, M., Ganeshan, S., Ansari, M. A., Alomary, M. N., Alyahya, S. A., Alghamdi, S. A., Almehmadi, M. M., Rajakumar, G., Thiruvengadam, M., & Vaiyapuri, M. (2021) · Journal of Saudi Chemical Society · doi:10.1016/j.jscs.2021.101319 · Cited by 44 · see citing works
“At the genetic level, PARP is in responsible of restoring single strand breaks (SSBs) triggered by the DNA damage or external stimuli, and also radiation [85].”
A Tale of Two Checkpoints: ATR Inhibition and PD-(L)1 Blockade
Ngoi, N. Y. L., Peng, G., & Yap, T. A. (2021) · Annual Review of Medicine · doi:10.1146/annurev-med-042320-025136 · Cited by 41 · see citing works
Sequential Administration of XPO1 and ATR Inhibitors Enhances Therapeutic Response in TP53-mutated Colorectal Cancer
Inoue, A., Robinson, F. S., Minelli, R., Tomihara, H., Rizi, B. S., Rose, J. L., Kodama, T., Srinivasan, S., Harris, A. L., Zuniga, A. M., et al. (2021) · Gastroenterology · doi:10.1053/j.gastro.2021.03.022 · Cited by 40 · see citing works
An Emerging Regulatory Role for the Tumor Microenvironment in the DNA Damage Response to Double-Strand Breaks
Lama-Sherpa, T. D., & Shevde, L. A. (2019) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-19-0665 · Cited by 36 · see citing works
“However, combination therapy is likely to yield a better response (102).”
Background
Immunology of Lynch Syndrome
Pastor, D. M., & Schlom, J. (2021) · Current Oncology Reports · doi:10.1007/s11912-021-01085-z · Cited by 35 · see citing works
Current and future immunotherapy approaches in ovarian cancer
Demircan, N. C., Boussios, S., Taşçı, T., & Öztürk, M. A. (2020) · Annals of Translational Medicine · doi:10.21037/atm-20-4499 · Cited by 33 · see citing works
“Presence of HR deficiencies like BRCA1/2 mutations cause amplification of TMB and contribute to ICI sensitivity (41,42).”
Treatment opportunities and future perspectives for pancreatic cancer patients with germline BRCA1-2 pathogenic variants
Macchini, M., Centonze, F., Peretti, U., Orsi, G., Militello, A. M., Valente, M. M., Cascinu, S., & Reni, M. (2021) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2021.102262 · Cited by 33 · see citing works
Immunotherapy for Cutaneous Squamous Cell Carcinoma: Results and Perspectives
Alberti, A., & Bossi, P. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2021.727027 · Cited by 33 · see citing works
“PARPi-mediated catastrophic DNA damage is a favorable factor for ICI therapy, and the relationship between tumor mutation burden and efficacy of ICI has been confirmed in previous studies (52).”
Result
Strategies for Heating Up Cold Tumors to Boost Immunotherapies
Zabransky, D. J., Yarchoan, M. M., & Jaffee, E. M. (2023) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-061421-040258 · Cited by 33 · see citing works
Ovarian cancer targeted therapy: current landscape and future challenges
Wang, G., Yang, H., Wang, Y., & Qin, J. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2025.1535235 · Cited by 32 · see citing works
“In ovarian cancer , PARPis have been shown to enhance the effects of immune checkpoint blockade ( 110), promoting tumor T-cell T-cell activation ( 111 ), which opens new”
The mutational pattern of homologous recombination (HR)-associated genes and its relevance to the immunotherapeutic response in gastric cancer
Fan, Y., Ying, H., Wu, X., Chen, H., Hu, Y., Zhang, H., Wu, L., Yang, Y., Mao, B., & Zheng, L. (2020) · Cancer Biology and Medicine · doi:10.20892/j.issn.2095-3941.2020.0089 · Cited by 32 · see citing works
Up-Regulation of PARP1 Expression Significantly Correlated with Poor Survival in Mucosal Melanomas
Donizy, P., Wu, C.-L., Mull, J., Fujimoto, M., Chłopik, A., Peng, Y. S., Shalin, S. C., Selim, M. A., Puig, S., Fernández‐Figueras, M. T., et al. (2020) · Cells · doi:10.3390/cells9051135 · Cited by 31 · see citing works
“Theoretically, PARPi could increase the clinical sensitivity of tumors to immunotherapy by increasing mutation burden and generating plenty of neoantigens [39].”
Background
Niraparib and dostarlimab for the treatment of recurrent platinum-resistant ovarian cancer: results of a Phase II study (MOONSTONE/GOG-3032)
Randall, L. M., O’Malley, D. M., Monk, B. J., Coleman, R. L., Gaillard, S. L., Adams, S. F., Duska, L., Dalton, H., Holloway, R. W., Huang, M. S., et al. (2023) · Gynecologic Oncology · doi:10.1016/j.ygyno.2023.10.005 · Cited by 30 · see citing works
RDGN-based predictive model for the prognosis of breast cancer
Dong, B., Yi, M., Luo, S., Li, A., & Wu, K. (2020) · Experimental Hematology and Oncology · doi:10.1186/s40164-020-00169-z · Cited by 29 · see citing works
Self-citation
Novel therapeutic combinations with PARP inhibitors for small cell lung cancer: A bench-to-bedside review
Xiong, J., Barayan, R., Louie, A. V., & Lok, B. H. (2022) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2022.07.008 · Cited by 30 · see citing works
The Emerging Role of Immunotherapy in Intrahepatic Cholangiocarcinoma
Fiste, O., Ntanasis‐Stathopoulos, I., Gavriatopoulou, M., Liontos, M., Koutsoukos, K., Dimopoulos, M. A., & Zagouri, F. (2021) · Vaccines · doi:10.3390/vaccines9050422 · Cited by 27 · see citing works
“Poly adenosine diphosphate-ribose polymerase inhibitors (PARPi) represent a novel class of targeted cancer therapy, by exploiting synthetic lethality in tumours which harbour germline and somatic alterations in DNA damage repair (DDR) genes; whereas their combination with immune-oncology appears to be a promising trea…”
Background
PARP Inhibitors in Melanoma—An Expanding Therapeutic Option?
Chan, W. Y., Brown, L. J., Reid, L., & Joshua, A. M. (2021) · Cancers · doi:10.3390/cancers13184520 · Cited by 29 · see citing works
“Highly mutated tumours often contain one or more mutations in key components of DDR pathways, such as BRCA1/2 for HR, MSH2 for MMR and POLE for DNA replication deficiency [17,35,48].”
BackgroundInfluential
Guanosine diphosphate–mannose suppresses homologous recombination repair and potentiates antitumor immunity in triple-negative breast cancer
Ding, J.-H., Xiao, Y., Yang, F., Song, X.-Q., Xu, Y., Ding, X.-H., Ding, R., Shao, Z., Di, G. H., & Jiang, Y. (2024) · Science Translational Medicine · doi:10.1126/scitranslmed.adg7740 · Cited by 27 · see citing works
“Preclinical research and early-phase clinical trials suggested that PARP inhibitors exhibit synergistic activity when administered in combination with ICIs ( 51 ).”
Background
Addressing Resistance to Immune Checkpoint Inhibitor Therapy: An Urgent Unmet Need
Hu‐Lieskovan, S., Malouf, G. G., Jacobs, I. A., Chou, J., Liu, L., & Johnson, M. L. (2021) · Future Oncology · doi:10.2217/fon-2020-0967 · Cited by 26 · see citing works
Low dose novel PARP-PI3K inhibition via nanoformulation improves colorectal cancer immunoradiotherapy
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“In addition to preventing the repair of DNA damage, PARP inhibitors play an activating role in the immunostimulatory cyclic GMP-AMP synthase–stimulator of interferon genes pathway [10].”
Background
Improving PARP inhibitor efficacy in high-grade serous ovarian carcinoma: A focus on the immune system
Bound, N. T., Vandenberg, C. J., Kartikasari, A. E. R., Plebanski, M., & Scott, C. L. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.886170 · Cited by 25 · see citing works
“A robust anti-tumour immune response relies on a cascade of interactions from the presentation of tumour-specific antigens, activation and trafficking of cytotoxic lymphocytes and the recognition and killing of tumour cells (Dunn et al., 2004a; Dunn et al., 2004b; Li et al., 2019).”
Background
Advanced Acral Melanoma Therapies: Current Status and Future Directions
Zhang, Y., Lan, S., & Wu, D. (2022) · Current Treatment Options in Oncology · doi:10.1007/s11864-022-01007-6 · Cited by 26 · see citing works
C/EBPβ promotes poly(ADP-ribose) polymerase inhibitor resistance by enhancing homologous recombination repair in high-grade serous ovarian cancer
Tan, J., Xu, Z., Li, M., Ye, F., Song, C., Xu, C., Zhang, X., Li, W., Wang, Y., Zeng, S., et al. (2021) · Oncogene · doi:10.1038/s41388-021-01788-4 · Cited by 24 · see citing works
“HR, an error-free form of repair with high fidelity, is crucial for cell survival [5, 21].”
BackgroundInfluential
Emerging strategies: PARP inhibitors in combination with immune checkpoint blockade in BRCA1 and BRCA2 mutation-associated and triple-negative breast cancer
Gupta, T., Vinayak, S., & Telli, M. L. (2022) · Breast Cancer Research and Treatment · doi:10.1007/s10549-022-06780-4 · Cited by 24 · see citing works
Strategies to synergize PD-1/PD-L1 targeted cancer immunotherapies to enhance antitumor responses in ovarian cancer
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Novel combinatorial strategies for boosting the efficacy of immune checkpoint inhibitors in advanced breast cancers
Tolba, M. F., Elghazaly, H. A., Bousoik, E., Elmazar, M. M., & Tolaney, S. M. (2021) · Clinical & Translational Oncology · doi:10.1007/s12094-021-02613-w · Cited by 22 · see citing works
“Several PARP inhibitors, including olaparib, niraparib and talazoparib, were developed principally for patients carrying BRCA1/2 mutations [43].”
Background
The landscape of circRNAs in gliomas temozolomide resistance: Insights into molecular pathways
Mafi, A., Hedayati, N., Kahkesh, S., Khoshayand, S., Alimohammadi, M., Farahani, N., & Hushmandi, K. (2024) · Non-coding RNA Research · doi:10.1016/j.ncrna.2024.05.010 · Cited by 22 · see citing works
“Inhibiting PARP with medicines like olaparib can stimulate neoantigen formation, upregulate PD-L1, enhance type I interferon signaling, and modify TME to enhance tumor suppressive responses when combined with ICI [38].”
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The impact of body composition on treatment in ovarian cancer: a current insight
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Immune Checkpoint Inhibitors and Other Immune Therapies in Breast Cancer: A New Paradigm for Prolonged Adjuvant Immunotherapy
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“This reprogramming induces the recruitment of T-cells into the tumor bed [102], thus transforming “cold tumors” into “hot tumors” through the activation of the immune response.”
Background
Therapeutic implications of germline vulnerabilities in DNA repair for precision oncology
Shah, S. M., Demidova, E. V., Lesh, R. W., Hall, M. J., Daly, M. B., Meyer, J. E., Edelman, M. J., & Arora, S. (2022) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2021.102337 · Cited by 16 · see citing works
PARP Inhibitors in the Neoadjuvant Setting; A Comprehensive Overview of the Rationale for their Use, Past and Ongoing Clinical Trials
Habaka, M., Daly, G. R., Shinyanbola, D., Alabdulrahman, M., McGrath, J., Dowling, G. P., Hehir, C. M., Huang, H. Y. R., Hill, A. D. K., Varešlija, D., et al. (2025) · Current Oncology Reports · doi:10.1007/s11912-025-01669-z · Cited by 17 · see citing works
“PARPi–ICI combinations may work by increasing the tumour’s neoantigen load, thereby enhancing immune recognition and response [93].”
Manipulating TGF-β signaling to optimize immunotherapy for cervical cancer
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Self-citation
The Potential of PARP Inhibitors as Antitumor Drugs and the Perspective of Molecular Design
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Mutation clearance and complete radiologic resolution of immunotherapy relapsed metastatic melanoma after treatment with nivolumab and olaparib in a patient with homologous recombinant deficiency: any role for PARP inhibitors and checkpoint blockade?
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Association of Homologous Recombination–DNA Damage Response Gene Mutations with Immune Biomarkers in Gastroesophageal Cancers
Cerniglia, M., Xiu, J., Grothey, A., Pishvaian, M. J., Baca, Y., Hwang, J. J., Marshall, J. L., VanderWalde, A. M., Shields, A. F., Lenz, H.-J., et al. (2021) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-20-0879 · Cited by 16 · see citing works
“DDR inhibition can also facilitate cell-intrinsic immunogenicity through upregulation of PD-L1, thereby making tumor cells visible to T cells via modulation of their cell-surface phenotype (36).”
Background
Targeting DNA Repair Response Promotes Immunotherapy in Ovarian Cancer: Rationale and Clinical Application
Xie, H., Wang, W., Qi, W.-C., Jin, W., & Xia, B. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.661115 · Cited by 17 · see citing works
“Type I IFN has a substantial influence on systemic immune response and promotes the maturation, migration, and activation of immune cells, especially DCs, natural killer cells, and T cells (Figure 1) (61, 62).”
Background
Advanced endometrial cancer—The next generation of treatment: A society of gynecologic oncology journal club clinical commentary
Tillmanns, T. D., Masri, A., Stewart, C. E., Chase, D. M., Karnezis, A. N., Chen, L.-M., & Urban, R. R. (2024) · Gynecologic Oncology Reports · doi:10.1016/j.gore.2024.101462 · Cited by 15 · see citing works
“It was hypothesized that combining poly(ADP-ribose) polymerase (PARP) inhibitor with an immune checkpoint inhibitor may improve outcomes in both dMMR and pMMR tumors (Lee and Konstantinopoulos, 2019; Li et al., 2019; Stewart et al., 2018; Wanderley et al., 2022).”
Background
New FDA oncology small molecule drugs approvals in 2020: Mechanism of action and clinical applications
Nogueira, T. C. M., & Souza, M. V. N. D. (2021) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2021.116340 · Cited by 15 · see citing works
The Prognostic and Therapeutic Potential of DNA Damage Repair Pathway Alterations and Homologous Recombination Deficiency in Lung Cancer
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Oregovomab: an investigational agent for the treatment of advanced ovarian cancer
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The biology of combination immunotherapy in recurrent metastatic head and neck cancer
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Self-citation
The effect and mechanism of astragalus polysaccharides on T cells and macrophages in inhibiting prostate cancer
Wu, C., Yang, Y., Lin, Y., Shu, L., Liu, H.-T., Lu, C., Wu, Y.-H., & Wu, Y.-H. (2024) · Biomedical Journal · doi:10.1016/j.bj.2024.100741 · Cited by 13 · see citing works
“Other research has reported PD-L1 expression in CRPC. Notably, studies have demonstrated the effectiveness of combining anti-PD-L1 therapy with treatments targeting myeloid-derived suppressor cells or PARP (poly ADP-ribose polymerase) inhibitors against CRPC [10].”
Clinical outcomes and longitudinal circulating tumor DNA changes after treatment with nivolumab and olaparib in immunotherapy relapsed melanoma with detected homologous recombination deficiencyPreprint
Khaddour, K., Ansstas, M., & Ansstas, G. (2021) · Molecular Case Studies · doi:10.1101/mcs.a006129 · Cited by 13 · see citing works
“In addition, there is mounting preclinical evidence of a synergistic role with combination ICB and PARP inhibitors to improve antitumor immunity (Li et al. 2019).”
Background
Efficacy and safety of immune checkpoint inhibitors for advanced or recurrent endometrial cancer: a systematic review and network meta-analysis
Huang, D., Su, L., Bai, Y., & Wang, Y. (2024) · BMC Cancer · doi:10.1186/s12885-024-13058-z · Cited by 12 · see citing works
“Additionally, PARP inhibitors have been found to enhance the priming and killing activity of T cells, thereby improving the response to ICIs [32].”
Background
High affinity and low PARP-trapping benzimidazole derivatives as a potential warhead for PARP1 degraders
Peng, X., Li, Y., Qu, J., Jiang, L., Wu, K., Liu, D., Chen, Y., Peng, J., Guo, Y., & Cao, X. (2024) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2024.116405 · Cited by 11 · see citing works
Self-citation
Targeting the DNA damage response in hematological malignancies
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Ginsenosides: Allies of gastrointestinal tumor immunotherapy
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Immunotherapy: Review of the Existing Evidence and Challenges in Breast Cancer
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“According to the literature, additional PARP inhibition could promote cross-presentation and modify the immune microenvironment for alleviating resistance as well as strengthening the efficacy exhibited by ICB therapy [62].”
Background
An imaging-guided self-amplifying photo-immunotherapeutic nanoparticle for STING pathway activation and enhanced cancer therapy
Chen, Q., Yu, H., Li, N., Zhang, H., Tan, M., Liu, W., Zheng, M., Hu, Y., Cheng, L., Chen, Y., et al. (2025) · Journal of Nanobiotechnology · doi:10.1186/s12951-025-03536-2 · Cited by 9 · see citing works
“By activating the STING pathway, it initiates a series of antitumor immune reactions, such as facilitating the maturation of DCs and amplifying the expression of related pro-inflammatory factors, thereby facilitating CTL activation and proliferation [44, 45].”
Ovarian cancer stem cells: Critical roles in anti-tumor immunity
Ding, J., Zhang, Y., & Che, Y. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.998220 · Cited by 9 · see citing works
“mutations are particularly effective in cancer cells (Li et al., 2019).”
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EREG is a risk factor for the prognosis of patients with cervical cancer
Li, T., Feng, R., Chen, B., & Zhou, J. (2023) · Frontiers in Medicine · doi:10.3389/fmed.2023.1161835 · Cited by 9 · see citing works
Photodynamic Immunotherapy Using ADU-S100-Modified Nanoparticles to Treat Triple-Negative Breast Cancer
Ge, T., Ge, W., Zhang, L., Yu, G., Li, Y., Sun, L., Fan, D., Yao, Z., Shi, L., & Wang, Y. (2023) · Nanomedicine · doi:10.2217/nnm-2022-0299 · Cited by 9 · see citing works
The relationship between the efficacy of talazoparib and the functional toll-like receptors 3 and 9 in triple negative breast cancer
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Design and synthesis of benzodiazepines as brain penetrating PARP-1 inhibitors
Jiang, Y. X., Gou, W., Shang, H., Cui, Y., Sun, X., Luo, L., Hou, W., Sun, T., & Li, Y. (2022) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.1080/14756366.2022.2053524 · Cited by 8 · see citing works
The molecular prognostic score, a classifier for risk stratification of high-grade serous ovarian cancer
Sarkar, S., Saha, S. A., Swarnakar, A., Chakrabarty, A., Dey, A., Sarkar, P., Banerjee, S., & Mitra, P. (2024) · Journal of Ovarian Research · doi:10.1186/s13048-024-01482-5 · Cited by 7 · see citing works
Research progress of immune checkpoint inhibitors in ovarian cancer
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In Situ Cancer Vaccines: Redefining Immune Activation in the Tumor Microenvironment
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Biomarker heterogeneity and efficacy of durvalumab plus carboplatin/paclitaxel followed by durvalumab with or without olaparib in patients with mismatch repair proficient endometrial cancer: exploratory analyses of the DUO-E/GOG-3041/ENGOT-EN10 trial
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Exploring the DNA damage response pathway for synthetic lethality
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Targeted Combination of Poly(ADP-ribose) Polymerase Inhibitors and Immune Checkpoint Inhibitors Lacking Evidence of Benefit: Focus in Ovarian Cancer
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“…enhancing immune activity has been suggested to be partly related to PARPi-mediated disruption of DNA repair and generation of DNA damage with a subsequent increase in neoantigen expression, which theoretically creates a more sensitive and favorable signal response (high TMB) to ICIs [38–40].”
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PARP inhibitors unleash the antitumor immune response
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The Synergistic Effect of PARP Inhibitors and Immune Checkpoint Inhibitors
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Role of PARP Inhibitors in Cancer Immunotherapy: Potential Friends to Immune Activating Molecules and Foes to Immune Checkpoints
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Potentiation of cancer immunogenicity by targeting PARP
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Targeting PARP1 to Enhance Anticancer Checkpoint Immunotherapy Response: Rationale and Clinical Implications
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Authors: Li, A., Yi, M., Qin, S., Chu, Q., Luo, S., & Wu, K.
Affiliations: Zhengzhou University (CN)
Tongji Hospital (CN)
Corresponding author: Luo, Suxia
Wu, Kongming
ORCID: Yi, Ming
Qin, Shuang
Chu, Qian
Luo, Suxia
Wu, Kongming
Venue: Journal of Hematology & Oncology
Publisher: Springer Science and Business Media LLC
Published: 2019-09-14
Volume: 12
Issue: 1
Pages: 98-98
ISSN: 1756-8722 (ISSN-L)
DOI: 10.1186/s13045-019-0784-8
PMC: PMC6744711
OpenAlex: W2972535107
Cited by: 143
References: 130
Citations by year: 2026: 10 · 2025: 14 · 2024: 14 · 2023: 16 · 2022: 21 · 2021: 36 · 2020: 30 · 2019: 2
FWCI: 2.17
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Journal of Hematology & Oncology (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Natural Science Foundation of China (81874120, 81572608, 81672984)
Wuhan Municipal Science and Technology Bureau (2017060201010170)
Topics: Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords: immune checkpoint blockade, PARP inhibitors, combination therapy, cancer immunotherapy, tumor immune microenvironment, PD-1, CTLA-4, immunosuppression, tumor immunogenicity, T cell priming, cross-presentation, drug resistance, cancer-immunity cycle
MeSH terms: Poly(ADP-ribose) Polymerase Inhibitors, Antineoplastic Agents, Humans, Immunotherapy, Poly(ADP-ribose) Polymerases

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Prospects for combining immune checkpoint blockade with PARP inhibition

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