Cited by 1,677Cancer Immunotherapy and BiomarkersT-cell and B-cell ImmunologyImmunotherapy and Immune Responses

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Up-Regulation of PD-L1, IDO, and T regs in the Melanoma Tumor Microenvironment Is Driven by CD8 + T Cells

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Spranger, Stefani, Spaapen, Robbert M., Zha, Yuanyuan, Williams, Jason, Meng, Yuru, Ha, Thanh T., Gajewski, Thomas F.·2013·Science Translational Medicine

DOI 10.1126/scitranslmed.3006504PMC PMC4136707

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Abstract

Tumor escape from immune-mediated destruction has been associated with immunosuppressive mechanisms that inhibit T cell activation. Although evidence for an active immune response, including infiltration with CD8(+) T cells, can be found in a subset of patients, those tumors are nonetheless not immunologically rejected. In the current report, we show that it is the subset of T cell-inflamed tumors that showed high expression of three defined immunosuppressive mechanisms: indoleamine-2,3-dioxygenase (IDO), PD-L1/B7-H1, and FoxP3(+) regulatory T cells (T(regs)), suggesting that these inhibitory pathways might serve as negative feedback mechanisms that followed, rather than preceded, CD8(+) T cell infiltration. Mechanistic studies in mice revealed that up-regulated expression of IDO and PD-L1, as well as recruitment of T(regs), in the tumor microenvironment depended on the presence of CD8(+) T cells. The former was driven by interferon-γ and the latter by a production of CCR4-binding chemokines along with a component of induced proliferation. Our results argue that these major immunosuppressive pathways are intrinsically driven by the immune system rather than being orchestrated by cancer cells, and imply that cancer immunotherapy approaches targeting negative regulatory immune checkpoints might be preferentially beneficial for patients with a preexisting T cell-inflamed tumor microenvironment.

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1 retracted

FOXO3 programs tumor-associated DCs to become tolerogenic in human and murine prostate cancer
Watkins, S. K., Zhu, Z., Riboldi, E., Shafer-Weaver, K., Stagliano, K. E., Sklavos, M. M., Ambs, S., Yagita∥, H., & Hurwitz, A. A. (2011) · Journal of Clinical Investigation · doi:10.1172/jci44325 · Cited by 137 · cited 1×
“Previous work has shown that antigen-presenting cells in the tumor microenvironment can be tolerogenic (37), and that some cytokines abundant in the tumor, such as IL-10, can inhibit dendritic cell activation and result in T cell anergy (38).”
Background
Retracted
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 · cited 1×
“…has been observed in the case of interleukin-2 (IL-2) for melanoma and kidney cancer (1), experimental cancer vaccines (2), and the recently U.S. Food and Drug Administration–approved agents Provenge for prostate cancer (3) and anti– CTLA-4 monoclonal antibody (mAb) (ipilimumab) for melanoma (4).”
Background
Safety, activity, and immune correlates of anti–PD-1 antibody in cancer
Topalian, S. L., Hodi, F. S., Brahmer, J. R., Gettinger, S. N., Smith, D. C., McDermott, D. F., Powderly, J. D., Carvajal, R. D., Sosman, J. A., Atkins, M. B., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200690 · Cited by 12,628
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
Sipuleucel-T Immunotherapy for Castration-Resistant Prostate Cancer
Kantoff, P. W., Higano, C. S., Shore, N. D., Berger, E. R., Small, E. J., Penson, D. F., Redfern, C. H., Ferrari, A. C., Dreicer, R., Sims, R. B., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1001294 · Cited by 5,572 · cited 1×
“…has been observed in the case of interleukin-2 (IL-2) for melanoma and kidney cancer (1), experimental cancer vaccines (2), and the recently U.S. Food and Drug Administration–approved agents Provenge for prostate cancer (3) and anti– CTLA-4 monoclonal antibody (mAb) (ipilimumab) for melanoma (4).”
Background
Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival
Curiel, T. J., Coukos, G., Zou, L., Alvarez, X., Cheng, P., Mottram, P., Evdemon-Hogan, M., Conejo-Garcia, J. R., Zhang, L., Burow, M., et al. (2004) · Nature Medicine · doi:10.1038/nm1093 · Cited by 5,151 · cited 1×
“Although direct CCL22 production by tumor cells in other cancer types also has been suggested (34), we did not detect CCL22 mRNA expression in a series of melanoma cell lines, arguing that in the melanoma context, it is likely derived from infiltrating nontumor stromal cells (13).”
Background
Phase I Study of Single-Agent Anti–Programmed Death-1 (MDX-1106) in Refractory Solid Tumors: Safety, Clinical Activity, Pharmacodynamics, and Immunologic Correlates
Brahmer, J. R., Drake, C. G., WOLLNER, I. S., Powderly, J. D., Picus, J., Sharfman, W. H., Stankevich, E., Pons, A., Salay, T. M., McMiller, T. L., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.26.7609 · Cited by 2,967 · cited 1×
“Clinical strategies to counter these immunosuppressive pathways are currently being evaluated, already with encouraging early-phase clinical trial results (10–12).”
Background
Prevention of Allogeneic Fetal Rejection by Tryptophan Catabolism
Munn, D. H., Zhou, M., Attwood, J. T., Bondarev, I. E., Conway, S. J., Marshall, B., Brown, C. C., & Mellor, A. L. (1998) · Science · doi:10.1126/science.281.5380.1191 · Cited by 2,589 · cited 1×
“IDO is a tryptophanmetabolizing enzyme that has been shown to contribute to peripheral immunologic tolerance (25).”
Background
Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase
Uyttenhove, C., Pilotte, L., Théate, I., Stroobant, V., Colau, D., Parmentier, N., Boon, T., & Van den Eynde, B. J. (2003) · Nature Medicine · doi:10.1038/nm934 · Cited by 2,305 · cited 1×
“…in mouse models include extrinsic suppression of CD8 + effector cells by CD4 + CD25 + FoxP3 + regulatory T cells (T regs ) (6), metabolic deregulation via tryptophan catabolism by indoleamine-2,3-dioxygenase (IDO) (7), and engagement of the inhibitory receptor PD-1 by the ligand PD-L1/B7-H1 (8, 9).”
Background
Colocalization of Inflammatory Response with B7-H1 Expression in Human Melanocytic Lesions Supports an Adaptive Resistance Mechanism of Immune Escape
Taube, J. M., Anders, R. A., Young, G. D., Xu, H., Sharma, R., McMiller, T. L., Chen, S., Klein, A. P., Pardoll, D. M., Topalian, S. L., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003689 · Cited by 2,157 · cited 2×
“It has been speculated that clinical response to antibodies targeting the PD-L1/PD-1 interaction may end up being restricted to cases in which PD-L1 expression is associated with a CD8 + T cell infiltrate and therefore is likely blunting host immunity (32).”
Background

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Spencer, K. R., Wang, J., Silk, A. W., Ganesan, S., Kaufman, H. L., & Mehnert, J. M. (2016) · American Society of Clinical Oncology Educational Book · doi:10.1200/edbk_160766 · Cited by 148
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“Some of the inhibitory interactions include programmed cell death 1 (PD-1) with its ligand PD-L1, and engagement of additional inhibitory receptors such as T cell immunoglobulin and mucin domain-containing-3 (HAVCR2 or TIM3) [129,130].”
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RIG-I activation is critical for responsiveness to checkpoint blockade
Heidegger, S. M., Wintges, A., Stritzke, F., Bek, S., Steiger, K., Koenig, P.-A., Göttert, S., Engleitner, T., Öllinger, R., Nedelko, T., et al. (2019) · Science Immunology · doi:10.1126/sciimmunol.aau8943 · Cited by 136
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Tucci, M., Passarelli, A. M., Mannavola, F., Felici, C., Stucci, L. S., Cives, M., & Silvestris, F. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.01148 · Cited by 139
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Background
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Background
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Fu, J. L., Malm, I., Kadayakkara, D. K. K., Levitsky, H., Pardoll, D. M., & Kim, Y. J. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-2685 · Cited by 124
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BackgroundInfluential
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Gupta, H. B., Clark, C. A., Yuan, B., Sareddy, G. R., Pandeswara, S., Padron, A. S., Hurez, V. J., Conejo-Garcia, J. R., Vadlamudi, R. K., Li, R., et al. (2016) · Signal Transduction and Targeted Therapy · doi:10.1038/sigtrans.2016.30 · Cited by 121
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Chen, R. Q., Liu, F., Qiu, X. Y., & Chen, X. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01503 · Cited by 123
“It is reported that PD-L1 upregulation in melanoma tumor microenvironment depends on CTL-secreted IFN-γ rather than cancer cells themselves (Gajewski et al., 2013; Spranger et al., 2013; Dong et al., 2017).”
Background
Ultrasound-Driven Biomimetic Nanosystem Suppresses Tumor Growth and Metastasis through Sonodynamic Therapy, CO Therapy, and Indoleamine 2,3-Dioxygenase Inhibition
Zhang, D., Lin, Z., Zheng, Y., Song, J., Li, J., Zeng, Y., & Liu, X. (2020) · ACS Nano · doi:10.1021/acsnano.0c03833 · Cited by 123
Radiotherapy induced immunogenic cell death by remodeling tumor immune microenvironment
Zhu, S., Wang, Y., Tang, J., & Cao, M. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1074477 · Cited by 137
mTORC1 upregulates B7-H3/CD276 to inhibit antitumor T cells and drive tumor immune evasion
Liu, H.-J., Du, H., Khabibullin, D., Zarei, M., Wei, K., Freeman, G. J., Kwiatkowski, D. J., & Henske, E. P. (2023) · Nature Communications · doi:10.1038/s41467-023-36881-7 · Cited by 125
Programmed death‐ligand 1 expression at tumor invasive front is associated with epithelial‐mesenchymal transition and poor prognosis in esophageal squamous cell carcinoma
Tsutsumi, S., Saeki, H., Nakashima, Y., Ito, S., Oki, E., Morita, M., Oda, Y., Okano, S., & Maehara, Y. (2017) · Cancer Science · doi:10.1111/cas.13237 · Cited by 122
Aberrant Expression of MHC Class II in Melanoma Attracts Inflammatory Tumor-Specific CD4+ T- Cells, Which Dampen CD8+ T-cell Antitumor Reactivity
Donia, M., Andersen, R. S., Kjeldsen, J. W., Fagone, P., Ahmad, S. M., Nicoletti, F., Andersen, M. H., Straten, P. T., & Svane, I. M. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-2956 · Cited by 120
Transforming Growth Factor β-Mediated Suppression of Antitumor T Cells Requires FoxP1 Transcription Factor Expression
Stephen, T. L., Rutkowski, M. R., Allegrezza, M. J., Perales‐Puchalt, A., Tesone, A. J., Svoronos, N., Nguyen, J. M., Sarmin, F., Borowsky, M. E., Tchou, J. C., et al. (2014) · Immunity · doi:10.1016/j.immuni.2014.08.012 · Cited by 120
Programmed Death-Ligand 1 Expression Predicts Tyrosine Kinase Inhibitor Response and Better Prognosis in a Cohort of Patients With Epidermal Growth Factor Receptor Mutation-Positive Lung Adenocarcinoma
Lin, C., Chen, X., Li, M., Liu, J., Qi, X., Yang, W., Zhang, H., Cai, Z., Dai, Y., & Ouyang, X. (2015) · Clinical Lung Cancer · doi:10.1016/j.cllc.2015.02.002 · Cited by 119
Mechanisms of resistance to immune checkpoint inhibitors in melanoma: What we have to overcome?
Ziogas, D. C., Theocharopoulos, C., Koutouratsas, T., Haanen, J. B. A. G., & Gogas, H. J. (2022) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2022.102499 · Cited by 122
PD-L1 up-regulation in melanoma increases disease aggressiveness and is mediated through miR-17-5p
Audrito, V., Serra, S., Stingi, A., Orso, F., Gaudino, F., Bologna, C., Neri, F., Garaffo, G., Nassini, R., Baroni, G., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.15213 · Cited by 118
Regorafenib Promotes Antitumor Immunity via Inhibiting PD-L1 and IDO1 Expression in Melanoma
Wu, R.-Y., Kong, P., Xia, L.-P., Huang, Y., Li, Z., Tang, Y.-Y., Chen, Y.-H., Li, X., Senthilkumar, R., Zhang, H., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-2840 · Cited by 116
Inhibition of Immunosuppressive Tumors by Polymer‐Assisted Inductions of Immunogenic Cell Death and Multivalent PD‐L1 Crosslinking
Li, L., Li, Y., Yang, C., Radford, D. C., Wang, J., Janat-Amsbury, M.-M., Kopec̆ek, J., & Yang, J. (2020) · Advanced Functional Materials · doi:10.1002/adfm.201908961 · Cited by 119
Targeting Innate Immunity in Cancer Therapy
Rameshbabu, S., Labadie, B. W., Argulian, A., & Patnaik, A. (2021) · Vaccines · doi:10.3390/vaccines9020138 · Cited by 121
“upregulate immune checkpoints, such as PD-1/PD-L1, within the TME, which directly suppress T cell effector mechanisms [13].”
Background
Targeting phosphatidylserine for Cancer therapy: prospects and challenges
Chang, W., Fa, H., Xiao, D., & Wang, J. (2020) · Theranostics · doi:10.7150/thno.45125 · Cited by 122
“For example, some patients have poor responses to PD-L1 inhibitors, which may be due to impaired T cell infiltration via upregulation of PD-L1, indoleamine2,3-dioxygenase (IDO), and FoxP3(+) regulatory T cells (Tregs), termed primary resistance [24] or due to”
Background
Activation of pyroptosis by specific organelle-targeting photodynamic therapy to amplify immunogenic cell death for anti-tumor immunotherapy
Zeng, S., Chen, C., Zhang, L., Liu, X., Qian, M., Cui, H., Wang, J., Chen, Q., & Peng, X. (2022) · Bioactive Materials · doi:10.1016/j.bioactmat.2022.07.016 · Cited by 117
Indoleamine 2,3-dioxygenase provides adaptive resistance to immune checkpoint inhibitors in hepatocellular carcinoma
Brown, Z. J., Yu, S. J., Heinrich, B., Ma, C., Fu, Q., Sandhu, M., Agdashian, D., Zhang, Q., Korangy, F., & Greten, T. F. (2018) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-018-2190-4 · Cited by 119
Impact of prior antibiotic use on the efficacy of nivolumab for non‑small cell lung cancer
Hakozaki, T., Okuma, Y., Omori, M., & Hosomi, Y. (2019) · Oncology Letters · doi:10.3892/ol.2019.9899 · Cited by 117
Pharmacological Modulation of the STING Pathway for Cancer Immunotherapy
Berger, G., Marloye, M., & Lawler, S. E. (2019) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2019.02.007 · Cited by 117
Photothermal-Chemotherapy Enhancing Tumor Immunotherapy by Multifunctional Metal–Organic Framework Based Drug Delivery System
Ni, W., Wu, J., Fang, H., Feng, Y., Hu, Y., Lin, L., Chen, J., Chen, F., & Tian, H. (2021) · Nano Letters · doi:10.1021/acs.nanolett.1c02782 · Cited by 116
Cell-state dynamics and therapeutic resistance in melanoma from the perspective of MITF and IFNγ pathways
Bai, X., Fisher, D. E., & Flaherty, K. T. (2019) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-019-0204-6 · Cited by 107
Multiplexed Immunohistochemistry for Molecular and Immune Profiling in Lung Cancer—Just About Ready for Prime-Time?
Hofman, P. M., Badoual, C., Henderson, F., Berland, L., Hamila, M., Long-Mira, É., Lassalle, S., Roussel, H., Hofman, V., Tartour, É., et al. (2019) · Cancers · doi:10.3390/cancers11030283 · Cited by 117
“This could be explained by the role of IFNγ produced by immune cells in regulating PD-L1 and IDO-1 in the tumor microenvironment [58].”
Background
Combination anti-PD-1 and anti-CTLA-4 therapy generates waves of clonal responses that include progenitor-exhausted CD8+ T cells
Wang, K., Coutifaris, P., Brocks, D., Wang, G., Azar, T., Solis, S., Nandi, A., Anderson, S., Han, N. A., Manne, S., et al. (2024) · Cancer Cell · doi:10.1016/j.ccell.2024.08.007 · Cited by 127
Non-invasive assessment of murine PD-L1 levels in syngeneic tumor models by nuclear imaging with nanobody tracers
Broos, K., Keyaerts, M., Lecocq, Q., Renmans, D., Nguyen, T. T., Escors, D., Liston, A., Raes, G., Breckpot, K., & Devoogdt, N. (2017) · Oncotarget · doi:10.18632/oncotarget.16708 · Cited by 115
PD-L1 and Emerging Biomarkers in Immune Checkpoint Blockade Therapy
Cottrell, T. R., & Taube, J. M. (2018) · The Cancer Journal · doi:10.1097/ppo.0000000000000301 · Cited by 118
A Three-in-One Immunotherapy Nanoweapon via Cascade-Amplifying Cancer-Immunity Cycle against Tumor Metastasis, Relapse, and Postsurgical Regrowth
Li, Q., Zhang, D., Zhang, J., Jiang, Y., Song, A., Li, Z., & Luan, Y. (2019) · Nano Letters · doi:10.1021/acs.nanolett.9b02923 · Cited by 113
Exosome-derived miR-142-5p remodels lymphatic vessels and induces IDO to promote immune privilege in the tumour microenvironment
Zhou, C., Zhang, Y., Yan, R.-M., Huang, L., Mellor, A. L., Yang, Y., Chen, X., Wei, W.-F., Wu, X., Yu, L., et al. (2020) · Cell Death and Differentiation · doi:10.1038/s41418-020-00618-6 · Cited by 115
Recent Advancements in Nanomedicine for ‘Cold’ Tumor Immunotherapy
Chen, Q., Sun, T., & Jiang, C. (2021) · Nano-Micro Letters · doi:10.1007/s40820-021-00622-6 · Cited by 115
Characterization of thein vivoimmune network of IDO, tryptophan metabolism, PD-L1, andCTLA-4in circulating immune cells in melanoma
Chevolet, I., Speeckaert, R., Schreuer, M. S., Neyns, B., Krysko, O., Bachert, C., Hennart, B., Allorge, D., van Geel, N., Gele, M. V., et al. (2015) · OncoImmunology · doi:10.4161/2162402x.2014.982382 · Cited by 113
Exceptional Response to Nivolumab and Stereotactic Body Radiation Therapy (SBRT) in Neuroendocrine Cervical Carcinoma with High Tumor Mutational Burden: Management Considerations from the Center For Personalized Cancer Therapy at UC San Diego Moores Cancer Center
Sharabi, A. B., Kim, S. S., Kato, S., Sanders, P. D., Patel, S. P., Sanghvi, P. R., Weihe, E., & Kurzrock, R. (2017) · The Oncologist · doi:10.1634/theoncologist.2016-0517 · Cited by 114
Rationally designed peptide-conjugated gold/platinum nanosystem with active tumor-targeting for enhancing tumor photothermal-immunotherapy
Yang, Q., Peng, J., Shi, K., Xiao, Y., Liu, Q., Han, R., Wei, X., & Qian, Z. (2019) · Journal of Controlled Release · doi:10.1016/j.jconrel.2019.06.031 · Cited by 113
CD40 stimulation as a molecular adjuvant for cancer vaccines and other immunotherapies
Bullock, T. N. J. (2021) · Cellular and Molecular Immunology · doi:10.1038/s41423-021-00734-4 · Cited by 117
The role of biomarkers in personalized immunotherapy
Sankar, K., Ye, J. C., Li, Z., Zheng, L., Song, W., & Hu-Lieskovan, S. (2022) · Biomarker Research · doi:10.1186/s40364-022-00378-0 · Cited by 111
The Expression and Prognostic Impact of Immune Cytolytic Activity-Related Markers in Human Malignancies: A Comprehensive Meta-analysis
Roufas, C., Chasiotis, D., Makris, A., Efstathiades, C., Dimopoulos, C., & Zaravinos, A. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00027 · Cited by 114
A single-cell atlas enables mapping of homeostatic cellular shifts in the adult human breast
Reed, A. D., Pensa, S., Steif, A., Stenning, J., Kunz, D. J., Porter, L. J., Hua, K., He, P., Twigger, A., Siu, A. J. Q., et al. (2024) · Nature Genetics · doi:10.1038/s41588-024-01688-9 · Cited by 131
“Previous studies have shown that high expression of IFNG in CD8 T cells, resembling what we observe in the CD8 T C1 cell population, can directly drive PDL1 expression in melanoma 38 , suggesting that this expansion of CD8 T C1 cells could be contributing to the PDL1 induction in HR donors.”
Result
Prognostic significance of programmed death-1 and programmed death-ligand 1 expression in patients with esophageal squamous cell carcinoma
Chen, K., Cheng, G., Zhang, F., Zhang, N., Li, D., Jin, J., Wu, J., Ying, L., Mao, W., & Su, D. (2016) · Oncotarget · doi:10.18632/oncotarget.8956 · Cited by 110
Enhanced killing of chordoma cells by antibody-dependent cell-mediated cytotoxicity employing the novel anti-PD-L1 antibody avelumab
Fujii, R., Friedman, E. R., Richards, J., Tsang, K. Y., Heery, C. R., Schlom, J., & Hodge, J. W. (2016) · Oncotarget · doi:10.18632/oncotarget.9256 · Cited by 110
Panaxadiol inhibits programmed cell death-ligand 1 expression and tumour proliferation via hypoxia-inducible factor (HIF)-1α and STAT3 in human colon cancer cells
Wang, Z., Li, M. Y., Zhang, Z. H., Zuo, H. X., Wang, J. Y., Xing, Y., Ri, M., Jin, H. L., Jin, C. H., Xu, G. H., et al. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.104727 · Cited by 110
Novel immune check point inhibiting antibodies in cancer therapy—Opportunities and challenges
Diesendruck, Y., & Benhar, I. (2017) · Drug Resistance Updates · doi:10.1016/j.drup.2017.02.001 · Cited by 107
Mechanisms of Drug Resistance in Melanoma
Winder, M. L., & Virós, A. (2017) · Handbook of experimental pharmacology · doi:10.1007/164_2017_17 · Cited by 112
PD-1 pathway and its clinical application: A 20 year journey after discovery of the complete human PD - 1 gene
Berger, K., & Pu, J. J. (2017) · Gene · doi:10.1016/j.gene.2017.09.050 · Cited by 113
Indoleamine 2,3-dioxygenase 1 (IDO1) activity in leukemia blasts correlates with poor outcome in childhood acute myeloid leukemia
Folgiero, V., Goffredo, B. M., Filippini, P., Masetti, R., Bonanno, G., Caruso, R., Bertaina, V., Mastronuzzi, A., Gaspari, S., Zecca, M., et al. (2013) · Oncotarget · doi:10.18632/oncotarget.1504 · Cited by 110
IDO inhibitors move center stage in immuno-oncology
Sheridan, C. (2015) · Nature Biotechnology · doi:10.1038/nbt0415-321 · Cited by 110
Mechanisms of Tumor Cell–Intrinsic Immune Evasion
Spranger, S., & Gajewski, T. F. (2017) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-030617-050606 · Cited by 113
An in situ hydrogel-mediated chemo-immunometabolic cancer therapy
Wang, B., Chen, J., Caserto, J. S., Wang, X., & Ma, M. (2022) · Nature Communications · doi:10.1038/s41467-022-31579-8 · Cited by 111
Mechanisms of Immune Tolerance in Leukemia and Lymphoma
Curran, E. K., Godfrey, J. K., & Kline, J. P. (2017) · Trends in Immunology · doi:10.1016/j.it.2017.04.004 · Cited by 108
Folic acid-functionalized polyethylenimine superparamagnetic iron oxide nanoparticles as theranostic agents for magnetic resonance imaging and PD-L1 siRNA delivery for gastric cancer
Luo, X., Peng, X., Hou, J., Wu, S., Shen, J., & Wang, L. (2017) · International Journal of Nanomedicine · doi:10.2147/ijn.s137245 · Cited by 108
Prognostic value of PDL1 expression in pancreatic cancer
Birnbaum, D. J., Finetti, P., Lopresti, A., Gilabert, M., Poizat, F., Turrini, O., Raoul, J., Delpéro, J., Moutardier, V., Birnbaum, D., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.11685 · Cited by 108
Uveal Versus Cutaneous Melanoma; Same Origin, Very Distinct Tumor Types
van der Kooij, M. K., Speetjens, F. M., van der Burg, S. H., & Kapiteijn, E. (2019) · Cancers · doi:10.3390/cancers11060845 · Cited by 107
“In the absence of a type 1 immune response, there is less interferon-gamma driven PD-L1 expression [128].”
Background
Immunotherapy of Cancer by Targeting Regulatory T cells
Chen, B.-J., Zhao, J., Zhang, D., Zheng, A.-H., & Wu, G. (2022) · International Immunopharmacology · doi:10.1016/j.intimp.2021.108469 · Cited by 107
A novel MDSC-induced PD-1 − PD-L1 + B-cell subset in breast tumor microenvironment possesses immuno-suppressive properties
Shen, M., Wang, J., Yu, W., Zhang, C., Liu, M., Wang, K., Yang, L., Wei, F., Wang, S. E., Sun, Q., et al. (2017) · OncoImmunology · doi:10.1080/2162402x.2017.1413520 · Cited by 104

Authors: Spranger, S., Spaapen, R. M., Zha, Y., Williams, J., Meng, Y., Ha, T. T., & Gajewski, T. F.
Affiliations: University of Chicago (US)
Corresponding author: Spranger, Stefani
Spaapen, Robbert M.
Gajewski, Thomas F.
ORCID: Spranger, Stefani
Spaapen, Robbert M.
Zha, Yuanyuan
Williams, Jason
Gajewski, Thomas F.
Venue: Science Translational Medicine
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2013-08-28
Volume: 5
Issue: 200
Pages: 200ra116-200ra116
ISSN: 1946-6234 (ISSN-L)
1946-6242
DOI: 10.1126/scitranslmed.3006504
PMC: PMC4136707
OpenAlex: W2136731993
Cited by: 1,677
References: 50
Citations by year: 2026: 49 · 2025: 76 · 2024: 112 · 2023: 122 · 2022: 136 · 2021: 173 · 2020: 158 · 2019: 162 · 2018: 171 · 2017: 176 · 2016: 155 · 2015: 111 · 2014: 70 · 2013: 6
FWCI: 61.01
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Science Translational Medicine (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Cancer Institute (R01CA127475, R01CA118153)
Topics: Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords: melanoma, tumor microenvironment, PD-L1, indoleamine 2,3-dioxygenase, regulatory T cells, CD8+ T cells, immunosuppression, immune checkpoint, interferon-gamma, cancer immunotherapy, tumor immune evasion
MeSH terms: Animals, Humans, Interferon-gamma, Lymphocyte Activation, Melanoma, Melanoma, Experimental, Neoplasm Metastasis, Up-Regulation, CD8-Positive T-Lymphocytes, Chemokines, Xenograft Model Antitumor Assays, Cell Proliferation, T-Lymphocytes, Regulatory, Mice, Forkhead Transcription Factors, Tumor Microenvironment, B7-H1 Antigen

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Up-Regulation of PD-L1, IDO, and T regs in the Melanoma Tumor Microenvironment Is Driven by CD8 + T Cells

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