The DOI matches its Crossref record; 128 of the 129 references it cites were found in a registry or an index.
The blockade of immune checkpoints in cancer immunotherapy
Open accessAbstract
Among the most promising approaches to activating therapeutic antitumour immunity is the blockade of immune checkpoints. Immune checkpoints refer to a plethora of inhibitory pathways hardwired into the immune system that are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues in order to minimize collateral tissue damage. It is now clear that tumours co-opt certain immune-checkpoint pathways as a major mechanism of immune resistance, particularly against T cells that are specific for tumour antigens. Because many of the immune checkpoints are initiated by ligand-receptor interactions, they can be readily blocked by antibodies or modulated by recombinant forms of ligands or receptors. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibodies were the first of this class of immunotherapeutics to achieve US Food and Drug Administration (FDA) approval. Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Recently, immunotherapies have shown promising results for reducing metastasis in melanoma or kidney cancer patients[1, 2].”
From Microfluidics: A New Tool for Modeling Cancer–Immune Interactions (2016) · cites this paper as [2]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Under normal physiological conditions, inhibitory immune checkpoint molecules are essential to maintain self-tolerance and prevent autoimmunity [1,2]”
From Characterizing the molecular regulation of inhibitory immune checkpoints with multimodal single-cell screens (2021) · cites this paper as [2]
In the citing paper
“there was strong down-regulation of several proteins with potential roles in modifying the response to immunotherapies exclusively in co-culture conditions, including CXCR4 (CD184), c-KIT (CD117) and KDR (CD309)23,24”
From Multimodal pooled Perturb-CITE-seq screens in patient models define mechanisms of cancer immune evasion (2021) · cites this paper as [23]
In the citing paper
“There is an active imbalance between stimulatory and inhibitory B7 family members in the tumor microenvironment [1,3,7,8].”
From T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment (2013) · cites this paper as [3]
In the citing paper
“Furthermore, TGF-β signaling in T cells activates SHP1 expression, which represses protein tyrosine kinase activities required for TCR signaling203,204.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [204]
In the citing paper
“In monotherapy, checkpoint inhibitors have resulted in impressive effects and durable responses in patients with highly refractory and late-stage cancers, such as metastatic melanoma and non-small cell lung cancer (NSCLC) [216].”
From Three decades of messenger RNA vaccine development (2019) · cites this paper as [216]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989
Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review
Wanchoo, R., Karam, S., Uppal, N. N., Barta, V. S., Deray, G., Devoe, C., Launay‐Vacher, V., Jhaveri, K. D., & on behalf of Cancer and Kidney International Network Workgroup on Immune Checkpoint Inhibitors (2017) · American Journal of Nephrology · doi:10.1159/000455014 · Cited by 15,320
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma
Hodi, F. S., O'Day, S. J., McDermott, D. F., Weber, R. W., Sosman, J. A., Haanen, J. B., Gonzalez, R., Robert, C., Schadendorf, D., Hassel, J. C., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1003466 · Cited by 15,155
Control of Regulatory T Cell Development by the Transcription Factor Foxp3
Hori, S., Nomura, T., & Sakaguchi, S. (2003) · Science · doi:10.1126/science.1079490 · Cited by 8,187
Foxp3 programs the development and function of CD4+CD25+ regulatory T cells
Fontenot, J. D., Gavin, M. A., & Rudensky, A. Y. (2003) · Nature Immunology · doi:10.1038/ni904 · Cited by 7,745
PD-1 and Its Ligands in Tolerance and Immunity
Keir, M. E., Butte, M. J., Freeman, G. J., & Sharpe, A. H. (2008) · Annual Review of Immunology · doi:10.1146/annurev.immunol.26.021607.090331 · Cited by 5,378
Freeman, G. J., Long, A. J., Iwai, Y., Bourque, K., Chernova, T., Nishimura, H., Fitz, L. J., Malenkovich, N., Okazaki, T., Byrne, M. C., et al. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.7.1027 · Cited by 5,294
Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion
Dong, H., Strome, S. E., Salomao, D. R., Tamura, H., Hirano, F., Flies, D. B., Roche, P. C., Lu, J., Zhu, G., Tamada, K., et al. (2002) · Nature Medicine · doi:10.1038/nm730 · Cited by 5,025
Restoring function in exhausted CD8 T cells during chronic viral infection
Barber, D. L., Wherry, E. J., Masopust, D., Zhu, B., Allison, J. P., Sharpe, A. H., Freeman, G. J., & Ahmed, R. (2005) · Nature · doi:10.1038/nature04444 · Cited by 4,057
Enhancement of Antitumor Immunity by CTLA-4 Blockade
Leach, D. R., Krummel, M. F., & Allison, J. P. (1996) · Science · doi:10.1126/science.271.5256.1734 · Cited by 3,955
Flagged first, then by citations
1 of the 129 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Taube, J. M. et al. B7-H1 expression co-localizes with inflammatory infiltrates in benign and malignant melanocytic lesions: implications for immunotherapy. Sci. Transl. Med. (In the press, 2012). Introduction of the adaptive immune resistance hypothesis that proposes that the expression of immune-checkpoint ligand by tumours can be induced by an antitumour immune response as an adaptive immune-protective mechanism.
Cited by
Sorted by citations
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989
Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer
Borghaei, H., Paz-Ares, L., Horn, L., Spigel, D. R., Steins, M., Ready, N. E., Chow, L. Q., Vokes, E. E., Felip, E., Holgado, E., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1507643 · Cited by 9,335
Nivolumab versus Docetaxel in Advanced Squamous-Cell Non–Small-Cell Lung Cancer
Brahmer, J., Reckamp, K. L., Baas, P., Crinò, L., Eberhardt, W. E. E., Poddubskaya, E., Antonia, S., Pluzanski, A., Vokes, E. E., Holgado, E., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1504627 · Cited by 8,447
Safety and activity of anti-PD-L1 antibody in patients with advanced cancer
Brahmer, J. R., Tykodi, S. S., Chow, L. Q. M., Hwu, W.-J., Topalian, S. L., Hwu, P., Drake, C. G., Camacho, L. H., Kauh, J., Odunsi, K., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200694 · Cited by 7,945
“All patients All doses 49 5 10 (3-22) 6 12 (5-25) 31 (17-45)”
InfluentialSelf-citationCancer immunotherapy using checkpoint blockade
Ribas, A., & Wolchok, J. D. (2018) · Science · doi:10.1126/science.aar4060 · Cited by 6,791
PD-1 blockade induces responses by inhibiting adaptive immune resistance
Tumeh, P. C., Harview, C. L., Yearley, J. H., Shintaku, I. P., Taylor, E. J. M., Robert, L., Chmielowski, B., Spasic, M., Henry, G., Ciobanu, V., et al. (2014) · Nature · doi:10.1038/nature13954 · Cited by 6,609
Herbst, R. S., Baas, P., Kim, D.-W., Felip, E., Pérez-Gracia, J. L., Han, J.-Y., Molina, J., Kim, J.-H., Arvis, C. D., Ahn, M.-J., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(15)01281-7 · Cited by 6,449
Pembrolizumab for the Treatment of Non–Small-Cell Lung Cancer
Garon, E. B., Rizvi, N. A., Hui, R., Leighl, N., Balmanoukian, A. S., Eder, J. P., Patnaik, A., Aggarwal, C., Gubens, M., Horn, L., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1501824 · Cited by 6,198
TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells
Li, T., Fan, J., Wang, B., Traugh, N. C., Chen, Q., Liu, J. S., Li, B., & Liu, X. S. (2017) · Cancer Research · doi:10.1158/0008-5472.can-17-0307 · Cited by 5,914
Pembrolizumab versus Ipilimumab in Advanced Melanoma
Robert, C., Schachter, J., Long, G. V., Arance, A., Grob, J. J., Mortier, L., Daud, A., Carlino, M. S., McNeil, C., Lotem, M., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1503093 · Cited by 5,887
Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy
Sharma, P., Hu-Lieskovan, S., Wargo, J. A., & Ribas, A. (2017) · Cell · doi:10.1016/j.cell.2017.01.017 · Cited by 5,588
Elements of cancer immunity and the cancer–immune set point
Chen, D. S., & Mellman, I. (2017) · Nature · doi:10.1038/nature21349 · Cited by 5,352
The future of immune checkpoint therapy
Sharma, P., & Allison, J. P. (2015) · Science · doi:10.1126/science.aaa8172 · Cited by 4,878
MicroRNA therapeutics: towards a new era for the management of cancer and other diseases
Rupaimoole, R., & Slack, F. J. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.246 · Cited by 4,741
Molecular and cellular insights into T cell exhaustion
Wherry, E. J., & Kurachi, M. (2015) · Nature Reviews Immunology · doi:10.1038/nri3862 · Cited by 4,652
Durvalumab after chemoradiotherapy in stage III non–small-cell lung cancer
Antonia, S. J., Villegas, A., Daniel, D., Vicente, D., Murakami, S., Hui, R., Yokoi, T., Chiappori, A., Lee, K. H., de Wit, M., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1709937 · Cited by 4,593
IFN-γ–related mRNA profile predicts clinical response to PD-1 blockade
Ayers, M., Lunceford, J., Nebozhyn, M., Murphy, E., Loboda, A., Kaufman, D. R., Albright, A., Cheng, J. D., Kang, S. P., Shankaran, V., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci91190 · Cited by 3,788
Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden
Chalmers, Z. R., Connelly, C. F., Fabrizio, D., Gay, L., Ali, S. M., Ennis, R., Schrock, A., Campbell, B., Shlien, A., Chmielecki, J., et al. (2017) · Genome Medicine · doi:10.1186/s13073-017-0424-2 · Cited by 3,519
Safety and Tumor Responses with Lambrolizumab (Anti–PD-1) in Melanoma
Hamid, O., Robert, C., DAUD, A. I., Hodi, F. S., Hwu, W., Kefford, R. F., Wolchok, J. D., Hersey, P., Joseph, R. W., Weber, J. S., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1305133 · Cited by 3,427
Lung cancer: current therapies and new targeted treatments
Hirsch, F. R., Scagliotti, G. V., Mulshine, J. L., Kwon, R., Curran, W. J., Wu, Y.-L. L. C., & Paz-Ares, L. G. (2016) · The Lancet · doi:10.1016/s0140-6736(16)30958-8 · Cited by 3,430
Mutations Associated with Acquired Resistance to PD-1 Blockade in Melanoma
Zaretsky, J. M., Garcia-Diaz, A., Shin, D. S., Escuin-Ordinas, H., Hugo, W., Hu-Lieskovan, S., Torrejon, D. Y., Abril-Rodriguez, G., Sandoval, S., Barthly, L., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1604958 · Cited by 3,237
Salgado, R., Denkert, C., Demaria, S., Sirtaine, N., Klauschen, F., Pruneri, G., Wienert, S., den Eynden, G. V., Baehner, F. L., Penault-Llorca, F. M., et al. (2014) · Annals of Oncology · doi:10.1093/annonc/mdu450 · Cited by 3,142
Molecular mechanisms of T cell co-stimulation and co-inhibition
Chen, L., & Flies, D. B. (2013) · Nature Reviews Immunology · doi:10.1038/nri3405 · Cited by 3,114
The prognostic landscape of genes and infiltrating immune cells across human cancers
Gentles, A. J., Newman, A. M., Liu, C. L., Bratman, S. V., Feng, W., Kim, D., Nair, V. S., Xu, Y., Khuong, A., Hoang, C. D., et al. (2015) · Nature Medicine · doi:10.1038/nm.3909 · Cited by 3,163
Fundamental Mechanisms of Immune Checkpoint Blockade Therapy
Wei, S. C., Duffy, C. R., & Allison, J. P. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-0367 · Cited by 3,088
Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease
Bianchini, G., Balko, J. M., Mayer, I. A., Sanders, M. E., & Gianni, L. (2016) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2016.66 · Cited by 3,079
Zhang, Y., & Zhang, Z. (2020) · Cellular and Molecular Immunology · doi:10.1038/s41423-020-0488-6 · Cited by 2,906
The PI3K Pathway in Human Disease
Fruman, D. A., Chiu, H., Hopkins, B. D., Bagrodia, S., Cantley, L. C., & Abraham, R. T. (2017) · Cell · doi:10.1016/j.cell.2017.07.029 · Cited by 2,749
Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy
Topalian, S. L., Taube, J. M., Anders, R. A., & Pardoll, D. M. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.36 · Cited by 2,733
Self-citationInfluence of tumour micro-environment heterogeneity on therapeutic response
Junttila, M. R., & de Sauvage, F. J. (2013) · Nature · doi:10.1038/nature12626 · Cited by 2,694
Development of tumor mutation burden as an immunotherapy biomarker: utility for the oncology clinic
Chan, T. A., Yarchoan, M., Jaffee, E., Swanton, C., Quezada, S. A., Stenzinger, A., & Peters, S. (2019) · Annals of Oncology · doi:10.1093/annonc/mdy495 · Cited by 2,683
Delivery technologies for cancer immunotherapy
Riley, R., June, C. H., Langer, R., & Mitchell, M. J. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-018-0006-z · Cited by 2,678
Triple-negative breast cancer molecular subtyping and treatment progress
Yin, L., Duan, J., Bian, X.-W., & Yu, S. (2020) · Breast Cancer Research · doi:10.1186/s13058-020-01296-5 · Cited by 2,473
iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics
Seymour, L., Bogaerts, J., Perrone, A., Ford, R., Schwartz, L. H., Mandrekar, S., Lin, N. U., Litière, S., Dancey, J., Chen, A., et al. (2017) · The Lancet Oncology · doi:10.1016/s1470-2045(17)30074-8 · Cited by 2,472
Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer
Twyman-Saint Victor, C., Rech, A. J., Maity, A., Rengan, R., Pauken, K. E., Stelekati, E., Benci, J. L., Xu, B., Dada, H., Odorizzi, P. M., et al. (2015) · Nature · doi:10.1038/nature14292 · Cited by 2,434
Comprehensive analyses of tumor immunity: implications for cancer immunotherapy
Li, B., Severson, E. A., Pignon, J., Zhao, H., Li, T., Novak, J. S. S., Jiang, P., Shen, H., Aster, J. C., Rodig, S. J., et al. (2016) · Genome biology · doi:10.1186/s13059-016-1028-7 · Cited by 2,432
Zou, W., Wolchok, J. D., & Chen, L. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aad7118 · Cited by 2,400
CTLA-4 and PD-1 Pathways: Similarities, Differences, and Implications of Their Inhibition
Buchbinder, E. I., & Desai, A. (2016) · American Journal of Clinical Oncology · doi:10.1097/coc.0000000000000239 · Cited by 2,360
“This has the potential to provide a more targeted signal with less unwanted toxicity, as selftolerance mediated through PD-1:PD-L2 interactions should be preserved.(37,49) Furthermore, as PD-L1 is known to bind CD80 as well as PD-1 to deliver inhibitory signals to T cells,(33) PDL1 inhibition with an appropriate antib…”
BackgroundSingle-cell reconstruction of the early maternal–fetal interface in humans
Vento-Tormo, R., Efremova, M., Botting, R. A., Turco, M. Y., Vento-Tormo, M., Meyer, K. B., Park, J.-E., Stephenson, E., Polański, K., Goncalves, A., et al. (2018) · Nature · doi:10.1038/s41586-018-0698-6 · Cited by 2,358
Pyroptosis: Mechanisms and Diseases
Yu, P., Zhang, X., Liu, N., Tang, L., Peng, C., & Chen, X. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00507-5 · Cited by 2,353
Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential
Sharma, P., & Allison, J. P. (2015) · Cell · doi:10.1016/j.cell.2015.03.030 · Cited by 2,345
PD-L1 expression as a predictive biomarker in cancer immunotherapy
Patel, S. P., & Kurzrock, R. (2015) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-14-0983 · Cited by 2,291
PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity
Gordon, S. R., Maute, R. L., Dulken, B. W., Hutter, G., George, B. M., McCracken, M. N., Gupta, R., Tsai, J. M., Sinha, R., Corey, D., et al. (2017) · Nature · doi:10.1038/nature22396 · Cited by 2,247
Topalian, S. L., Sznol, M., McDermott, D. F., Kluger, H. M., Carvajal, R. D., Sharfman, W. H., Brahmer, J. R., Lawrence, D. P., Atkins, M. B., Powderly, J. D., et al. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2013.53.0105 · Cited by 2,222
Self-citationNon–Small Cell Lung Cancer: Epidemiology, Screening, Diagnosis, and Treatment
Duma, N., Santana-Dávila, R., & Molina, J. R. (2019) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2019.01.013 · Cited by 2,296
Noman, M. Z., Desantis, G., Janji, B., Hasmim, M., Karray, S., Dessen, P., Bronte, V., & Chouaib, S. (2014) · Journal of Experimental Medicine · doi:10.1084/jem.20131916 · Cited by 2,166
Roles of the immune system in cancer: From tumor initiation to metastatic progression
Gonzalez, H., Hagerling, C., & Werb, Z. (2018) · Genes & Development · doi:10.1101/gad.314617.118 · Cited by 2,111
Development of therapeutic antibodies for the treatment of diseases
Lu, R., Hwang, Y., Liu, I.-J., Lee, C., Tsai, H.-Z., Li, H., & Wu, H. (2020) · Journal of Biomedical Science · doi:10.1186/s12929-019-0592-z · Cited by 2,235
Irradiation and anti–PD-L1 treatment synergistically promote antitumor immunity in mice
Deng, L., Liang, H. L., Burnette, B., Beckett, M., Darga, T. E., Weichselbaum, R. R., & Fu, Y. (2014) · Journal of Clinical Investigation · doi:10.1172/jci67313 · Cited by 2,119
Cancer immunotherapy via dendritic cells
Palucka, K., & Banchereau, J. (2012) · Nature reviews. Cancer · doi:10.1038/nrc3258 · Cited by 2,109
Defining T Cell States Associated with Response to Checkpoint Immunotherapy in Melanoma
Sade-Feldman, M., Yizhak, K., Bjorgaard, S. L., Ray, J. P., de Boer, C. G., Jenkins, R. W., Lieb, D. J., Chen, J. H., Frederick, D. T., Barzily-Rokni, M., et al. (2018) · Cell · doi:10.1016/j.cell.2018.10.038 · Cited by 2,053
Chiappinelli, K. B., Strissel, P. L., Desrichard, A., Li, H., Henke, C., Akman, B., Hein, A., Rote, N. S., Cope, L. M., Snyder, A., et al. (2015) · Cell · doi:10.1016/j.cell.2015.07.011 · Cited by 2,022
Self-citationThe diverse functions of the PD1 inhibitory pathway
Sharpe, A. H., & Pauken, K. E. (2017) · Nature reviews. Immunology · doi:10.1038/nri.2017.108 · Cited by 2,054
Tumor microenvironment as a therapeutic target in cancer
Xiao, Y. Q., & Yu, D. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107753 · Cited by 2,026
Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens
Gubin, M. M., Zhang, X., Schuster, H., Caron, E., Ward, J. P., Noguchi, T., Ivanova, Y., Hundal, J., Arthur, C. D., Krebber, W.-J., et al. (2014) · Nature · doi:10.1038/nature13988 · Cited by 1,974
Molecular therapies and precision medicine for hepatocellular carcinoma
Llovet, J. M., Montal, R., Sia, D., & Finn, R. S. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-018-0073-4 · Cited by 1,965
Non-small cell lung cancer: current treatment and future advances
Zappa, C., & Mousa, S. A. (2016) · Translational Lung Cancer Research · doi:10.21037/tlcr.2016.06.07 · Cited by 1,944
Interferon Receptor Signaling Pathways Regulating PD-L1 and PD-L2 Expression
Garcia-Diaz, A., Shin, D. S., Moreno, B. H., Saco, J., Escuin-Ordinas, H., Rodriguez, G. A., Zaretsky, J. M., Sun, L., Hugo, W., Wang, X., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.04.031 · Cited by 1,942
Cortés, J., Cescon, D. W., Rugo, H. S., Nowecki, Z. I., Im, S., Yusof, M. M., Gallardo, C., Lipatov, O., Barrios, C. H., Holgado, E., et al. (2020) · The Lancet · doi:10.1016/s0140-6736(20)32531-9 · Cited by 1,847
Nanotechnology for Multimodal Synergistic Cancer Therapy
Fan, W., Yung, B. C., Huang, P., & Chen, X. S. (2017) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00258 · Cited by 1,813
Robert, C., Ribas, A., Wolchok, J. D., Hodi, F. S., Hamid, O., Kefford, R., Weber, J. S., Joshua, A. M., Hwu, W.-J., Gangadhar, T. C., et al. (2014) · The Lancet · doi:10.1016/s0140-6736(14)60958-2 · Cited by 1,774
Seiwert, T. Y., Burtness, B., Mehra, R., Weiss, J., Berger, R., Eder, J. P., Heath, K., McClanahan, T., Lunceford, J., Gause, C., et al. (2016) · The Lancet Oncology · doi:10.1016/s1470-2045(16)30066-3 · Cited by 1,745
Alsaab, H. O., Sau, S., Alzhrani, R. M., Tatiparti, K., Bhise, K., Kashaw, S. K., & Iyer, A. K. (2017) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00561 · Cited by 1,750
Fibroblast Heterogeneity and Immunosuppressive Environment in Human Breast Cancer
Costa, A., Kieffer, Y., Scholer-Dahirel, A., Pelon, F., Bourachot, B., Cardon, M., Sirven, P., Magagna, I., Fuhrmann, L., Bernard, C., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.01.011 · Cited by 1,705
T cell costimulatory receptor CD28 is a primary target for PD-1–mediated inhibition
Hui, E., Cheung, J., Zhu, J., Su, X., Taylor, M. J., Wallweber, H. A., Sasmal, D. K., Huang, J., Kim, J. M., Mellman, I., et al. (2017) · Science · doi:10.1126/science.aaf1292 · Cited by 1,689
Hallmarks of response, resistance, and toxicity to immune checkpoint blockade
Morad, G., Helmink, B. A., Sharma, P., & Wargo, J. A. (2021) · Cell · doi:10.1016/j.cell.2021.09.020 · Cited by 1,648
Phenotype molding of stromal cells in the lung tumor microenvironment
Lambrechts, D., Wauters, E., Boeckx, B., Aibar, S., Nittner, D., Burton, O., Bassez, A., Decaluwé, H., Pircher, A., Van den Eynde, K., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0096-5 · Cited by 1,648
Chen, Q., Xu, L., Liang, C., Wang, C., Peng, R., & Liu, Z. (2016) · Nature Communications · doi:10.1038/ncomms13193 · Cited by 1,612
Combining immunotherapy and targeted therapies in cancer treatment
Vanneman, M. W., & Dranoff, G. (2012) · Nature reviews. Cancer · doi:10.1038/nrc3237 · Cited by 1,627
Koyama, S., Akbay, E. A., Li, Y. Y., Herter-Sprie, G. S., Buczkowski, K. A., Richards, W. G., Gandhi, L., Redig, A. J., Rodig, S. J., Asahina, H., et al. (2016) · Nature Communications · doi:10.1038/ncomms10501 · Cited by 1,580
Ribas, A., Puzanov, I. J., Dummer, R., Schadendorf, D., Hamid, O., Robert, C., Hodi, F. S., Schachter, J., Pavlick, A. C., Lewis, K. D., et al. (2015) · The Lancet Oncology · doi:10.1016/s1470-2045(15)00083-2 · Cited by 1,590
PD-L1 as a biomarker of response to immune-checkpoint inhibitors
Doroshow, D. B., Bhalla, S., Beasley, M. B., Sholl, L. M., Kerr, K. M., Gnjatic, S., Wistuba, I. I., Rimm, D. L., Tsao, M. S., & Hirsch, F. R. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00473-5 · Cited by 1,575
Organoid modeling of the tumor immune microenvironment
Neal, J. T., Li, X., Zhu, J., Giangarra, V., Grzeskowiak, C. L., Ju, J., Liu, I. H., Chiou, S.-H., Salahudeen, A. A., Smith, A. R., et al. (2018) · Cell · doi:10.1016/j.cell.2018.11.021 · Cited by 1,556
Regulatory T cells in cancer immunosuppression — implications for anticancer therapy
Togashi, Y., Shitara, K., & Nishikawa, H. (2019) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-019-0175-7 · Cited by 1,620
Oncolytic virotherapy promotes intratumoral T cell infiltration and improves anti-PD-1 immunotherapy
Ribas, A., Dummer, R., Puzanov, I., VanderWalde, A., Andtbacka, R. H. I., Michielin, O., Olszanski, A. J., Malvehy, J., Cebon, J., Fernandez, E., et al. (2017) · Cell · doi:10.1016/j.cell.2017.08.027 · Cited by 1,520
Yang, G., Xu, L., Chao, Y., Xu, J., Sun, X., Wu, Y., Peng, R., & Liu, Z. (2017) · Nature Communications · doi:10.1038/s41467-017-01050-0 · Cited by 1,491
Tumour-intrinsic resistance to immune checkpoint blockade
Kalbasi, A. K., & Ribas, A. (2019) · Nature reviews. Immunology · doi:10.1038/s41577-019-0218-4 · Cited by 1,525
Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies
Naidoo, J., Page, D. B., Li, B. T., Connell, L. C., Schindler, K., Lacouture, M. E., Postow, M. A., & Wolchok, J. D. (2015) · Annals of Oncology · doi:10.1093/annonc/mdv383 · Cited by 1,505
Llosa, N. J., Cruise, M., Tam, A., Wicks, E. C., Hechenbleikner, E. M., Taube, J. M., Blosser, R. L., Fan, H., Wang, H., Luber, B. S., et al. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-0863 · Cited by 1,487
Self-citationPembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study
Nanda, R., Chow, L. Q. M., Dees, E. C., Berger, R., Gupta, S., Geva, R., Pusztai, L., Pathiraja, K., Aktan, G., Cheng, J. D., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2015.64.8931 · Cited by 1,477
Disease-Associated Microglia: A Universal Immune Sensor of Neurodegeneration
Deczkowska, A., Keren-Shaul, H., Weiner, A., Colonna, M., Schwartz, M., & Amit, I. (2018) · Cell · doi:10.1016/j.cell.2018.05.003 · Cited by 1,474
Macrophages and Therapeutic Resistance in Cancer
Ruffell, B., & Coussens, L. M. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.02.015 · Cited by 1,474
Mittal, D., Gubin, M. M., Schreiber, R. D., & Smyth, M. J. (2014) · Current Opinion in Immunology · doi:10.1016/j.coi.2014.01.004 · Cited by 1,471
CD8+ T cell states in human cancer: insights from single-cell analysis
van der Leun, A. M., Thommen, D. S., & Schumacher, T. N. (2020) · Nature reviews. Cancer · doi:10.1038/s41568-019-0235-4 · Cited by 1,487
Rizvi, N. A., Mazières, J., Planchard, D., Stinchcombe, T. E., Dy, G. K., Antonia, S. J., Horn, L., Lena, H., Minenza, E., Mennecier, B., et al. (2015) · The Lancet Oncology · doi:10.1016/s1470-2045(15)70054-9 · Cited by 1,415
Classifying Cancers Based on T-cell Infiltration and PD-L1
Teng, M. W. L., Ngiow, S. F., Ribas, A., & Smyth, M. J. (2015) · Cancer Research · doi:10.1158/0008-5472.can-15-0255 · Cited by 1,436
Role of tumor microenvironment in tumorigenesis
Wang, M., Zhao, J., Zhang, L., Wei, F., Lian, Y., Wu, Y., Gong, Z., Zhang, S., Zhou, J., Cao, K., et al. (2017) · Journal of Cancer · doi:10.7150/jca.17648 · Cited by 1,404
PD-L1 Expression in Triple-Negative Breast Cancer
Mittendorf, E. A., Philips, A. V., Meric‐Bernstam, F., Qiao, N., Wu, Y., Harrington, S. M., Su, X., Wang, Y., Gonzalez-Angulo, A. M., Akçakanat, A., et al. (2014) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-13-0127 · Cited by 1,420
Mechanisms of resistance to immune checkpoint inhibitors
Jenkins, R. W., Barbie, D. A., & Flaherty, K. T. (2018) · British Journal of Cancer · doi:10.1038/bjc.2017.434 · Cited by 1,383
A review of cancer immunotherapy toxicity
Kennedy, L. B., & Salama, A. K. S. (2020) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21596 · Cited by 1,396
Immune Checkpoint Inhibitors in Cancer Therapy
Shiravand, Y., Khodadadi, F., Kashani, S. M. A., Hosseini-Fard, S. R., Hosseini, S., Sadeghirad, H., Ladwa, R., O’Byrne, K., & Kulasinghe, A. (2022) · Current Oncology · doi:10.3390/curroncol29050247 · Cited by 1,353
Primary Resistance to PD-1 Blockade Mediated by JAK1/2 Mutations
Shin, D. S., Zaretsky, J. M., Escuin-Ordinas, H., Garcia-Diaz, A., Hu-Lieskovan, S., Kalbasi, A., Grasso, C. S., Hugo, W., Sandoval, S., Torrejon, D. Y., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-1223 · Cited by 1,337
Self-citationBalar, A. V., Castellano, D., O’Donnell, P. H., Grivas, P. D., Vuky, J., Powles, T. B., Plimack, E. R., Hahn, N. M., de Wit, R., Pang, L., et al. (2017) · The Lancet Oncology · doi:10.1016/s1470-2045(17)30616-2 · Cited by 1,351
Davoli, T., Uno, H., Wooten, E. C., & Elledge, S. J. (2017) · Science · doi:10.1126/science.aaf8399 · Cited by 1,347
Chaput, N., Lepage, P., Coutzac, C., Soularue, E., Le Roux, K., Monot, C., Boselli, L., Routier, E., Cassard, L., Collins, M., et al. (2017) · Annals of Oncology · doi:10.1093/annonc/mdx108 · Cited by 1,310
Type I interferons in anticancer immunity
Zitvogel, L., Galluzzi, L., Kepp, O., Smyth, M. J., & Kroemer, G. (2015) · Nature Reviews Immunology · doi:10.1038/nri3845 · Cited by 1,305
Distinct cellular mechanisms underlie anti-CTLA-4 and anti-PD-1 checkpoint blockade
Wei, S. C., Levine, J. H., Cogdill, A. P., Zhao, Y., Anang, N.-A. A. S., Andrews, M. C., Sharma, P., Wang, J., Wargo, J. A., Pe’er, D., et al. (2017) · Cell · doi:10.1016/j.cell.2017.07.024 · Cited by 1,302
Combination cancer immunotherapy and new immunomodulatory targets
Mahoney, K. M., Rennert, P. D., & Freeman, G. J. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4591 · Cited by 1,294
Genomic spectra of biliary tract cancer
Nakamura, H. K., Arai, Y., Totoki, Y., Shirota, T., Elzawahry, A., Kato, M., Hama, N., Hosoda, F., Urushidate, T., Ohashi, S., et al. (2015) · Nature Genetics · doi:10.1038/ng.3375 · Cited by 1,306
PD-1 Blockade with pembrolizumab in advanced Merkel-cell carcinoma
Nghiem, P. T., Bhatia, S., Lipson, E. J., Kudchadkar, R. R., Miller, N. J., Annamalai, L., Berry, S., Chartash, E. K., Daud, A., Fling, S. P., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1603702 · Cited by 1,258
Self-citation
Metadata
- Authors
- Pardoll, D. M.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Pardoll, Drew M.
- ORCID
- Pardoll, Drew M.
- Venue
- Nature Reviews Cancer
- Published
- 2012-03-22
- Volume
- 12
- Issue
- 4
- Pages
- 252-264
- ISSN
- 1474-175X (ISSN-L)
- 1474-1768
- PMC
- PMC4856023
- OpenAlex
- W2066671159
- Cited by
- 13,838
- References
- 129
- Citations by year
- 2026: 652 · 2025: 910 · 2024: 1153 · 2023: 1202 · 2022: 1302 · 2021: 1456 · 2020: 1409 · 2019: 1236 · 2018: 1197 · 2017: 1146 · 2016: 897 · 2015: 647 · 2014: 339 · 2013: 240 · 2012: 39
- FWCI
- 41.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature reviews. Cancer (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Melanoma Research Alliance
- Hussman Foundation
- National Cancer Institute (P30CA021765, P30CA006973)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- immune checkpoint, cancer immunotherapy, immune checkpoint blockade, CTLA-4, PD-1, tumor immune evasion, antitumor immunity, self-tolerance, ligand-receptor interactions, antibody therapy, combination therapy, immune resistance
- MeSH terms
- Animals, Antigens, Neoplasm, Clinical Trials as Topic, Humans, Immunotherapy, Neoplasms, Tumor Escape, Cancer Vaccines, Molecular Targeted Therapy, CTLA-4 Antigen, Programmed Cell Death 1 Receptor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
