Up-Regulation of PD-L1, IDO, and T regs in the Melanoma Tumor Microenvironment Is Driven by CD8 + T Cells
Open accessAbstract
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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Metastatic melanoma patients receiving vaccine and cytokine therapies show two broad tumor phenotypes: T cell-inflamed and non-T cell-inflamed.
“Tumor analysis from patients with metastatic melanoma receiving vaccine and cytokine therapies suggested a paradigm of two broad phenotypes characterized by the presence or absence a T cell-inflamed tumor.”
From Reimagining IDO Pathway Inhibition in Cancer Immunotherapy via Downstream Focus on the Tryptophan–Kynurenine–Aryl Hydrocarbon Axis (2019) · cites this paper as [7]
Tumors in patients who have sustained responses to checkpoint inhibitors mostly show a T cell-inflamed microenvironment before or early in treatment.
“Tumors from patients showing sustained treatment response predominately demonstrate a T cell-inflamed tumor microenvironment prior to, or early on, treatment.”
From Reimagining IDO Pathway Inhibition in Cancer Immunotherapy via Downstream Focus on the Tryptophan–Kynurenine–Aryl Hydrocarbon Axis (2019) · cites this paper as [7]
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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 132 · see citing works
RetractedImproved 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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Curran, M. A., Montalvo, W., Yagita, H., & Allison, J. P. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0915174107 · Cited by 1,874 · see citing works
A function for interleukin 2 in Foxp3-expressing regulatory T cells
Fontenot, J. D., Rasmussen, J. P., Gavin, M. A., & Rudensky, A. Y. (2005) · Nature Immunology · doi:10.1038/ni1263 · Cited by 1,819 · see citing works
Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma
Parsa, A. T., Waldron, J. S., Panner, A., Crane, C. A., Parney, I. F., Barry, J. J., Cachola, K. E., Murray, J. C., Tihan, T., Jensen, M. C., et al. (2006) · Nature Medicine · doi:10.1038/nm1517 · Cited by 1,341 · see citing works
Fuertes, M. B., Kacha, A. K., Kline, J., Woo, S.-R., Kranz, D. M., Murphy, K. M., & Gajewski, T. F. (2011) · Journal of Experimental Medicine · doi:10.1084/jem.20101159 · Cited by 1,192 · see citing works
Self-citationTumor Rejection After Direct Costimulation of CD8 + T Cells by B7-Transfected Melanoma Cells
Townsend, S. E., & Allison, J. P. (1993) · Science · doi:10.1126/science.7678351 · Cited by 1,136 · see citing works
Chemokine expression in melanoma metastases associated with CD8+ T-cell recruitment
Harlin, H., Meng, Y., Peterson, A. C., Zha, Y., Tretiakova, M., Slingluff, C., McKee, M., & Gajewski, T. F. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-2281 · Cited by 1,121 · see citing works
Characterization of circulating T cells specific for tumor-associated antigens in melanoma patients
Lee, P. P., Yee, C., Savage, P. A., Fong, L. H., Brockstedt, D. G., Weber, J. S., Johnson, D. L., Swetter, S. M., Thompson, J. A., Greenberg, P. D., et al. (1999) · Nature Medicine · doi:10.1038/9525 · Cited by 1,117 · see citing works
Type I interferon is selectively required by dendritic cells for immune rejection of tumors
Diamond, M. S., Kinder, M., Matsushita, H., Mashayekhi, M., Dunn, G. P., Archambault, J. M., Lee, H., Arthur, C. D., White, J. M., Kalinke, U., et al. (2011) · Journal of Experimental Medicine · doi:10.1084/jem.20101158 · Cited by 1,081 · see citing works
Chen, L., Ashe, S., Brady, W. A., Hellström, I., Hellström, K. E., Ledbetter, J. A., McGowan, P., & Linsley, P. S. (1992) · Cell · doi:10.1016/s0092-8674(05)80059-5 · Cited by 1,050 · see citing works
Iellem, A., Mariani, M., Lang, R., Recalde, H. R., Panina‐Bordignon, P., Sinigaglia, F., & D’Ambrosio, D. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.194.6.847 · Cited by 915 · see citing works
Blank, C., Brown, I., Peterson, A. C., Spiotto, M., Iwai, Y., Honjo, T., & Gajewski, T. F. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-3259 · Cited by 772 · see citing works
An immune-active tumor microenvironment favors clinical response to ipilimumab
Ji, R., Chasalow, S. D., Wang, L., Hamid, O., Schmidt, H., Cogswell, J. P., Alaparthy, S., Berman, D., Jure‐Kunkel, M., Siemers, N. O., et al. (2011) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-011-1172-6 · Cited by 771 · see citing works
Erdag, G., Schaefer, J. T., Smolkin, M. E., Deacon, D. H., Shea, S. M., Dengel, L. T., Patterson, J. W., & Slingluff, C. L. (2012) · Cancer Research · doi:10.1158/0008-5472.can-11-3218 · Cited by 591 · see citing works
Selective inhibition of IDO1 effectively regulates mediators of antitumor immunity
Liu, X., Shin, N., Koblish, H. K., Yang, G., Wang, Q., Wang, K., Leffet, L., Hansbury, M., Thomas, B. A., Rupar, M. J., et al. (2010) · Blood · doi:10.1182/blood-2009-09-246124 · Cited by 549 · see citing works
Atkins, M. B., Kunkel, L., Sznol, M., & Rosenberg, S. A. (2000) · PubMed · Cited by 515 · see citing works
Steinbrink, K., Jonuleit, H., Müller, G., Schuler, G., Knop, J., & Enk, A. (1999) · Blood · doi:10.1182/blood.v93.5.1634 · Cited by 509 · see citing works
Messina, J. L., Fenstermacher, D. A., Eschrich, S., Qu, X., Berglund, A. E., Lloyd, M. C., Schell, M. J., Sondak, V. K., Weber, J. S., & Mulé, J. J. (2012) · Scientific Reports · doi:10.1038/srep00765 · Cited by 426 · see citing works
PD-1/PD-L1 interactions inhibit antitumor immune responses in a murine acute myeloid leukemia model
Zhang, L., Gajewski, T. F., & Kline, J. P. (2009) · Blood · doi:10.1182/blood-2009-03-206672 · Cited by 409 · see citing works
Lee, I. T., Wang, L., Wells, A. D., Dorf, M. E., Özkaynak, E., & Hancock, W. W. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20041709 · Cited by 371 · see citing works
B7-H1 pathway and its role in the evasion of tumor immunity
Dong, H., & Chen, L. (2003) · Journal of Molecular Medicine · doi:10.1007/s00109-003-0430-2 · Cited by 276 · see citing works
Immune Suppression in the Tumor Microenvironment
Gajewski, T. F., Meng, Y., & Harlin, H. (2006) · Journal of Immunotherapy · doi:10.1097/01.cji.0000199193.29048.56 · Cited by 261 · see citing works
Schwartz, R. H. (1997) · Current Opinion in Immunology · doi:10.1016/s0952-7915(97)80081-7 · Cited by 256 · see citing works
Munn, D. H., & Mellor, A. L. (2003) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2003.11.003 · Cited by 256 · see citing works
Gajewski, T. F., Louahed, J., & Brichard, V. G. (2010) · The Cancer Journal · doi:10.1097/ppo.0b013e3181eacbd8 · Cited by 250 · see citing works
Sipuleucel-T Immunotherapy for Castration-Resistant Prostate Cancer
Tanimoto, T., Hori, A., & Kami, M. (2010) · New England Journal of Medicine · doi:10.1056/nejmc1009982 · Cited by 203 · see citing works
Mortarini, R., Piris, A., Maurichi, A., Molla, A., Bersani, I., Bono, A. V., Bartoli, C., Santinami, M., Lombardo, C., Ravagnani, F., et al. (2003) · PubMed · Cited by 177 · see citing works
Transient T cell depletion causes regression of melanoma metastases
Rasku, M. A., Clem, A. L., Telang, S., Taft, B. S., Gettings, K. F., Gragg, H., Cramer, D. E., Lear, S. C., McMasters, K. M., Miller, D. M., et al. (2008) · Journal of Translational Medicine · doi:10.1186/1479-5876-6-12 · Cited by 158 · see citing works
Peterson, A., Harlin, H., & Gajewski, T. F. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.12.144 · Cited by 153 · see citing works
Appay, V., Jandus, C., Voelter, V., Reynard, S., Coupland, S. E., Rimoldi, D., Líénard, D., Guillaume, P., Krieg, A. Μ., Cerottini, J., et al. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.3.1670 · Cited by 150 · see citing works
Harlin, H., Kuna, T. V., Peterson, A., Meng, Y., & Gajewski, T. F. (2006) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-005-0118-2 · Cited by 143 · see citing works
Hoelzinger, D. B., Smith, S. E., Mirza, N. N., Dominguez, A. L., Manrique, S. Z., & Lustgarten, J. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0904084 · Cited by 111 · see citing works
Naturally Arising CD25+CD4+ Regulatory T Cells in Tumor Immunity
Nomura, T., & Sakaguchi, S. (2005) · Springer eBooks · doi:10.1007/3-540-27702-1_13 · Cited by 92 · see citing works
Brown, I. E., Blank, C., Kline, J., Kacha, A. K., & Gajewski, T. F. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.7.4521 · Cited by 91 · see citing works
Homeostatic Proliferation Plus Regulatory T-Cell Depletion Promotes Potent Rejection of B16 Melanoma
Kline, J. P., Brown, I. E., Zha, Y.-Y., Blank, C. U., Strickler, J. H., Wouters, H., Zhang, L., & Gajewski, T. F. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-4696 · Cited by 89 · see citing works
Chen, S., Pham-Nguyen, K. B., Martinet, O., Huang, Y., Yang, W., Thung, S. N., Chen, L., Mittler, R. S., & Woo, S. L. C. (2000) · Molecular Therapy · doi:10.1006/mthe.2000.0086 · Cited by 87 · see citing works
Sznol, M., Powderly, J. D., Smith, D. C., Brahmer, J. R., Drake, C. G., McDermott, D. F., Lawrence, D. P., Wolchok, J. D., Topalian, S. L., & Lowy, I. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2010.28.15_suppl.2506 · Cited by 85 · see citing works
Frequent cytolytic T-cell responses to peptide MAGE-A10(254-262) in melanoma.
Valmori, D., Dutoit, V., Rubio‐Godoy, V., Chambaz, C., Liénard, D., Guillaume, P., Romero, P. J., Cerottini, J. C., & Rimoldi, D. (2001) · PubMed · Cited by 72 · see citing works
Induction of Cytotoxic Granules in Human Memory CD8+ T Cell Subsets Requires Cell Cycle Progression
Meng, Y., Harlin, H., O’Keefe, J. P., & Gajewski, T. F. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.3.1981 · Cited by 57 · see citing works
Blank, C. A., Brown, I. E., Kacha, A. K., Markiewicz, M. A., & Gajewski, T. F. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.6.3416 · Cited by 34 · see citing works
Gajewski, T. F., Zha, Y., Thurner, B., & Schuler, G. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.27.15_suppl.9002 · Cited by 31 · see citing works
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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 · see citing works
Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients
Herbst, R. S., Soria, J.-C., Kowanetz, M., Fine, G. D., Hamid, O., Gordon, M. S., Sosman, J. A., McDermott, D. F., Powderly, J. D., Gettinger, S. N., et al. (2014) · Nature · doi:10.1038/nature14011 · Cited by 5,231 · see citing works
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 · see citing works
Immune Checkpoint Blockade: A Common Denominator Approach to Cancer Therapy
Topalian, S. L., Drake, C. G., & Pardoll, D. M. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.03.001 · Cited by 4,229 · see citing works
Innate and adaptive immune cells in the tumor microenvironment
Gajewski, T. F., Schreiber, H., & Fu, Y.-X. (2013) · Nature Immunology · doi:10.1038/ni.2703 · Cited by 4,148 · see citing works
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 · see citing works
Commensal <i>Bifidobacterium</i> promotes antitumor immunity and facilitates anti–PD-L1 efficacy
Sivan, A., Corrales, L., Hubert, N., Williams, J. B., Aquino-Michaels, K., Earley, Z. M., Benyamin, F. W., Man Lei, Y., Jabri, B., Alegre, M.-L., et al. (2015) · Science · doi:10.1126/science.aac4255 · Cited by 3,888 · see citing works
Self-citationMolecular and genetic properties of tumors associated with local immune cytolytic activity
Rooney, M. S., Shukla, S. A., Wu, C. J., Getz, G., & Hacohen, N. (2015) · Cell · doi:10.1016/j.cell.2014.12.033 · Cited by 3,825 · see citing works
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 · see citing works
Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity
Spranger, S., Bao, R., & Gajewski, T. F. (2015) · Nature · doi:10.1038/nature14404 · Cited by 2,830 · see citing works
Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards
Bronte, V., Brandau, S., Chen, S.-H., Colombo, M. P., Frey, A. B., Greten, T. F., Mandruzzato, S., Murray, P. J., Ochoa, A., Ostrand-Rosenberg, S., et al. (2016) · Nature Communications · doi:10.1038/ncomms12150 · Cited by 2,751 · see citing works
Tumor and Microenvironment Evolution during Immunotherapy with Nivolumab
Riaz, N., Havel, J. J., Makarov, V., Desrichard, A., Urba, W. J., Sims, J. S., Hodi, F. S., Martín-Algarra, S., Mandal, R., Sharfman, W. H., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.028 · Cited by 2,401 · see citing works
Self-citationZou, W., Wolchok, J. D., & Chen, L. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aad7118 · Cited by 2,382 · see citing works
The immune contexture in cancer prognosis and treatment
Fridman, W. H., Zitvogel, L., Sautès–Fridman, C., & Kroemer, G. (2017) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2017.101 · Cited by 2,263 · see citing works
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 2,101 · see citing works
STING-Dependent Cytosolic DNA Sensing Mediates Innate Immune Recognition of Immunogenic Tumors
Woo, S.-R., Fuertes, M. B., Corrales, L., Spranger, S., Furdyna, M. J., Leung, M. Y. K., Duggan, R., Wang, Y., Barber, G. N., Fitzgerald, K. A., et al. (2014) · Immunity · doi:10.1016/j.immuni.2014.10.017 · Cited by 1,917 · see citing works
Predictive biomarkers for checkpoint inhibitor-based immunotherapy
Gibney, G. T., Weiner, L. M., & Atkins, M. B. (2016) · The Lancet Oncology · doi:10.1016/s1470-2045(16)30406-5 · Cited by 1,635 · see citing works
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 1,580 · see citing works
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 1,553 · see citing works
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 · see citing works
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 · see citing works
Anti–PD-1/PD-L1 therapy of human cancer: past, present, and future
Chen, L., & Han, X. N. (2015) · Journal of Clinical Investigation · doi:10.1172/jci80011 · Cited by 1,433 · see citing works
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 · see citing works
Steeg, P. S. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.25 · Cited by 1,363 · see citing works
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 1,394 · see citing works
Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution
McGranahan, N., Rosenthal, R., Hiley, C. T., Rowan, A. J., Watkins, T. B. K., Wilson, G. A., Birkbak, N. J., Veeriah, S., Van Loo, P., Herrero, J., et al. (2017) · Cell · doi:10.1016/j.cell.2017.10.001 · Cited by 1,298 · see citing works
Zhu, Y., Knolhoff, B. L., Meyer, M. A., Nywening, T. M., West, B. L., Luo, J., Wang-Gillam, A., Goedegebuure, S. P., Linehan, D. C., & DeNardo, D. G. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-3723 · Cited by 1,324 · see citing works
Acquired Resistance to Fractionated Radiotherapy Can Be Overcome by Concurrent PD-L1 Blockade
Dovedi, S. J., Adlard, A. L., Lipowska‐Bhalla, G., McKenna, C., Jones, S., Cheadle, E. J., Stratford, I. J., Poon, E., Morrow, M., Stewart, R. A., et al. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-1258 · Cited by 1,316 · see citing works
Cloughesy, T. F., Mochizuki, A. Y., Orpilla, J. R., Hugo, W., Lee, A. H., Davidson, T. B., Wang, A. C., Ellingson, B. M., Rytlewski, J. A., Sanders, C. M., et al. (2019) · Nature Medicine · doi:10.1038/s41591-018-0337-7 · Cited by 1,382 · see citing works
Targeted agents and immunotherapies: optimizing outcomes in melanoma
Luke, J. J., Flaherty, K. T., Ribas, A., & Long, G. V. (2017) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2017.43 · Cited by 1,243 · see citing works
Tumor Interferon Signaling Regulates a Multigenic Resistance Program to Immune Checkpoint Blockade
Benci, J. L., Xu, B., Qiu, Y., Wu, T. J., Dada, H., Twyman-Saint Victor, C., Cucolo, L., Lee, D. S. M., Pauken, K. E., Huang, A. C., et al. (2016) · Cell · doi:10.1016/j.cell.2016.11.022 · Cited by 1,216 · see citing works
Roles of IFN-γ in tumor progression and regression: A review
Jorgovanovic, D., Song, M., Wang, L., & Zhang, Y. (2020) · Biomarker Research · doi:10.1186/s40364-020-00228-x · Cited by 1,234 · see citing works
Multimodal Analysis of Composition and Spatial Architecture in Human Squamous Cell Carcinoma
Ji, A. L., Rubin, A. J., Thrane, K., Jiang, S., Reynolds, D. L., Meyers, R. M., Guo, M. G., George, B. M., Mollbrink, A., Bergenstråhle, J., et al. (2020) · Cell · doi:10.1016/j.cell.2020.05.039 · Cited by 1,117 · see citing works
“This model is consistent with shared recruitment chemokines between CD8 T cells and Tregs (Figure 4F) as well as CD8 T cell requirement for Treg-mediated suppression (Spranger et al., 2013).”
ResultOvercoming T cell exhaustion in infection and cancer
Pauken, K. E., & Wherry, E. J. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.02.008 · Cited by 1,178 · see citing works
Immune Escape Mechanisms as a Guide for Cancer Immunotherapy
Beatty, G. L., & Gladney, W. L. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-1860 · Cited by 1,078 · see citing works
Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition
Cherkassky, L., Morello, A., Villena‐Vargas, J., Feng, Y., Dimitrov, D. S., Jones, D. R., Sadelain, M., & Adusumilli, P. S. (2016) · Journal of Clinical Investigation · doi:10.1172/jci83092 · Cited by 1,075 · see citing works
IDO in the Tumor Microenvironment: Inflammation, Counter-Regulation, and Tolerance
Munn, D. H., & Mellor, A. L. (2016) · Trends in Immunology · doi:10.1016/j.it.2016.01.002 · Cited by 1,054 · see citing works
Pitt, J. M., Vétizou, M., Daillère, R., Roberti, M. P., Yamazaki, T., Routy, B., Lepage, P., Boneca, I. G., Chamaillard, M., Kroemer, G., et al. (2016) · Immunity · doi:10.1016/j.immuni.2016.06.001 · Cited by 1,040 · see citing works
Long, G. V., Dummer, R., Hamid, O., Gajewski, T. F., Caglevic, C., Dalle, S., Arance, A., Carlino, M. S., Grob, J.-J., Kim, T. M., et al. (2019) · The Lancet Oncology · doi:10.1016/s1470-2045(19)30274-8 · Cited by 960 · see citing works
Clinical relevance of host immunity in breast cancer: from TILs to the clinic
Savas, P., Salgado, R., Denkert, C., Sotiriou, C., Darcy, P. K., Smyth, M. J., & Loi, S. (2016) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2015.215 · Cited by 890 · see citing works
Juneja, V. R., McGuire, K. A., Manguso, R. T., LaFleur, M. W., Collins, N. B., Haining, W. N., Freeman, G. J., & Sharpe, A. H. (2017) · The Journal of Experimental Medicine · doi:10.1084/jem.20160801 · Cited by 848 · see citing works
Chemokines and the immune response to cancer
Ozga, A. J., Chow, M. T., & Luster, A. D. (2021) · Immunity · doi:10.1016/j.immuni.2021.01.012 · Cited by 846 · see citing works
Recurrent Glioblastoma Treated with Recombinant Poliovirus
Desjardins, A., Gromeier, M., Herndon, J. E., Beaubier, N. T., Bolognesi, D. P., Friedman, A. H., Friedman, H. S., McSherry, F., Muscat, A. M., Nair, S. K., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1716435 · Cited by 821 · see citing works
Hendry, S. A., Salgado, R., Gevaert, T., Russell, P. A., John, T., Thapa, B., Christie, M., de Vijver, K. K. V., Estrada, M. V., Ericsson, P. I. G., et al. (2017) · Advances in Anatomic Pathology · doi:10.1097/pap.0000000000000161 · Cited by 803 · see citing works
Regulation of PD-L1: a novel role of pro-survival signalling in cancer.
Chen, J., Jiang, C. C., Jin, L., & Zhang, X. D. (2016) · Annals of Oncology · doi:10.1093/annonc/mdv615 · Cited by 767 · see citing works
Ferrara, R., Mezquita, L., Texier, M., Lahmar, J., Audigier-Valette, C., Tessonnier, L., Mazieres, J., Zalcman, G., Brosseau, S., Le Moulec, S., et al. (2018) · JAMA Oncology · doi:10.1001/jamaoncol.2018.3676 · Cited by 720 · see citing works
Programmed death ligand-1 expression in non-small cell lung cancer
Velcheti, V., Schalper, K. A., Carvajal, D. E., Anagnostou, V., Syrigos, K. N., Sznol, M., Herbst, R. S., Gettinger, S. N., Chen, L., & Rimm, D. L. (2013) · Laboratory Investigation · doi:10.1038/labinvest.2013.130 · Cited by 752 · see citing works
IFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer
Abiko, K., Matsumura, N., Hamanishi, J., Horikawa, N., Murakami, R., Yamaguchi, K., Yoshioka, Y., Baba, T., Konishi, I., & Mandai, M. (2015) · British Journal of Cancer · doi:10.1038/bjc.2015.101 · Cited by 725 · see citing works
De-novo and acquired resistance to immune checkpoint targeting
Syn, N. L. X., Teng, M. W. L., Mok, T. S. K., & Soo, R. A. (2017) · The Lancet Oncology · doi:10.1016/s1470-2045(17)30607-1 · Cited by 742 · see citing works
Zamarin, D., Holmgaard, R. B., Subudhi, S. K., Park, J. S., Mansour, M., Palese, P., Merghoub, T., Wolchok, J. D., & Allison, J. P. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3008095 · Cited by 711 · see citing works
Vaccines for established cancer: overcoming the challenges posed by immune evasion
van der Burg, S. H., Arens, R., OSSENDORP, F. A., van Hall, T., & Melief, C. J. M. (2016) · Nature reviews. Cancer · doi:10.1038/nrc.2016.16 · Cited by 709 · see citing works
Hendry, S. A., Salgado, R., Gevaert, T., Russell, P. A., John, T., Thapa, B., Christie, M., de Vijver, K. K. V., Estrada, M. V., Ericsson, P. I. G., et al. (2017) · Advances in Anatomic Pathology · doi:10.1097/pap.0000000000000162 · Cited by 707 · see citing works
Neoantigen vaccine: an emerging tumor immunotherapy
Miao, P., Mo, Y., Wang, Y., Wu, P., Zhang, Y., Xiong, F., Guo, C. J., Wu, S., Li, Y., Li, X., et al. (2019) · Molecular Cancer · doi:10.1186/s12943-019-1055-6 · Cited by 701 · see citing works
Immunity, inflammation, and cancer: an eternal fight between good and evil.
Shalapour, S., & Karin, M. (2015) · Journal of Clinical Investigation · doi:10.1172/jci80007 · Cited by 641 · see citing works
DNA Damage and Repair Biomarkers of Immunotherapy Response
Mouw, K. W., Goldberg, M. S., Konstantinopoulos, P. A., & D’Andrea, A. D. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-0226 · Cited by 652 · see citing works
Immune escape to PD-L1/PD-1 blockade: seven steps to success (or failure)
Kim, J. M., & Chen, D. S. (2016) · Annals of Oncology · doi:10.1093/annonc/mdw217 · Cited by 648 · see citing works
Evolving synergistic combinations of targeted immunotherapies to combat cancer
Melero, I., Berman, D. M., Aznar, M. A., Korman, A. J., Perez‐Gracia, J. L., & Haanen, J. B. A. G. (2015) · Nature reviews. Cancer · doi:10.1038/nrc3973 · Cited by 633 · see citing works
Italiano, A., Soria, J., Toulmonde, M., Michot, J., Lucchesi, C., Varga, A., Coindre, J., Blakemore, S. J., Clawson, A., Suttle, B. B., et al. (2018) · The Lancet Oncology · doi:10.1016/s1470-2045(18)30145-1 · Cited by 637 · see citing works
Clinical blockade of PD1 and LAG3 — potential mechanisms of action
Nguyen, L. T., & Ohashi, P. S. (2014) · Nature reviews. Immunology · doi:10.1038/nri3790 · Cited by 621 · see citing works
Adaptive Immune Resistance: How Cancer Protects from Immune Attack
Ribas, A. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-0563 · Cited by 620 · see citing works
Recent advancements in liposome technology
Filipczak, N., Pan, J., Yalamarty, S. S. K., & Torchilin, V. P. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.06.022 · Cited by 604 · see citing works
Combination Immunotherapy with CAR T Cells and Checkpoint Blockade for the Treatment of Solid Tumors
Grosser, R., Cherkassky, L., Chintala, N., & Adusumilli, P. S. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.09.006 · Cited by 603 · see citing works
PD-L1 expression and prognostic impact in glioblastoma
Nduom, E. K.-E., Wei, J., Yaghi, N. K., Huang, N., Kong, L.-Y., Gabrusiewicz, K. R., Ling, X., Zhou, S., Ivan, C., Chen, J. Q., et al. (2015) · Neuro-Oncology · doi:10.1093/neuonc/nov172 · Cited by 600 · see citing works
PD-1 and PD-L1 expression in molecularly selected non-small-cell lung cancer patients
D’Incecco, A., Andreozzi, M., Ludovini, V., Rossi, E., Capodanno, A., Landi, L. M., Tibaldi, C., Minuti, G., Salvini, J., Coppi, E., et al. (2014) · British Journal of Cancer · doi:10.1038/bjc.2014.555 · Cited by 594 · see citing works
Cutaneous melanoma: From pathogenesis to therapy (Review)
Leonardi, G. C., Falzone, L., Salemi, R., Zanghì, A., Spandidos, D. A., McCubrey, J. A., Candido, S., & Libra, M. (2018) · International Journal of Oncology · doi:10.3892/ijo.2018.4287 · Cited by 594 · see citing works
Schmittnaegel, M., Rigamonti, N., Kadioglu, E., Cassará, A., Wyser Rmili, C., Kiialainen, A., Kienast, Y., Mueller, H.-J., Ooi, C.-H., Laoui, D., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aak9670 · Cited by 582 · see citing works
Multidimensional communication in the microenvirons of glioblastoma
Broekman, M. L. D., Maas, S. L. N., Abels, E. R., Mempel, T. R., Krichevsky, A. M., & Breakefield, X. O. (2018) · Nature Reviews Neurology · doi:10.1038/s41582-018-0025-8 · Cited by 574 · see citing works
Combination Cancer Therapy with Immune Checkpoint Blockade: Mechanisms and Strategies
Patel, S. A., & Minn, A. J. (2018) · Immunity · doi:10.1016/j.immuni.2018.03.007 · Cited by 574 · see citing works
Resistance to PD1/PDL1 checkpoint inhibition
O’Donnell, J. S., Long, G. V., Scolyer, R. A., Teng, M. W. L., & Smyth, M. J. (2016) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2016.11.007 · Cited by 574 · see citing works
Innate Immune Recognition of Cancer
Woo, S., Corrales, L. P., & Gajewski, T. F. (2015) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032414-112043 · Cited by 569 · see citing works
Huang, A. C. C., & Zappasodi, R. (2022) · Nature Immunology · doi:10.1038/s41590-022-01141-1 · Cited by 573 · see citing works
Regulatory circuits of T cell function in cancer
Speiser, D. E., Ho, P., & Verdeil, G. (2016) · Nature reviews. Immunology · doi:10.1038/nri.2016.80 · Cited by 559 · see citing works
Spranger, S., Koblish, H. K., Horton, B., Scherle, P. A., Newton, R., & Gajewski, T. F. (2014) · Journal for ImmunoTherapy of Cancer · doi:10.1186/2051-1426-2-3 · Cited by 552 · see citing works
Self-citationImmunotherapy Converts Nonimmunogenic Pancreatic Tumors into Immunogenic Foci of Immune Regulation
Lutz, E. R., Wu, A. A., Bigelow, E. O., Sharma, R. B., Mo, G., Soares, K. C., Solt, S., Dorman, A., Wamwea, A., Yager, A., et al. (2014) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-14-0027 · Cited by 551 · see citing works
PD-L1 expression and tumor mutational burden are independent biomarkers in most cancers
Yarchoan, M. M., Albacker, L. A., Hopkins, A. C., Montesion, M., Murugesan, K., Vithayathil, T., Zaidi, N., Azad, N. S., Laheru, D. A., Frampton, G. M., et al. (2019) · JCI Insight · doi:10.1172/jci.insight.126908 · Cited by 554 · see citing works
Liu, Y., Liang, X., Dong, W., Fang, Y., Lv, J., Zhang, T., Fiskesund, R., Xie, J., Liu, J., Yin, X., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.02.005 · Cited by 535 · see citing works
In situ activation of platelets with checkpoint inhibitors for post-surgical cancer immunotherapy
Wang, C., Sun, W., Ye, Y., Hu, Q., Bomba, H. N., & Gu, Z. (2017) · Nature Biomedical Engineering · doi:10.1038/s41551-016-0011 · Cited by 528 · see citing works
Roles of regulatory T cells in cancer immunity
Takeuchi, Y., & Nishikawa, H. (2016) · International Immunology · doi:10.1093/intimm/dxw025 · Cited by 517 · see citing works
Ott, P. A., Élez, E., Hiret, S., Kim, D., Morosky, A., Saraf, S., Piperdi, B., & Mehnert, J. M. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2017.72.5069 · Cited by 520 · see citing works
Immune suppressive mechanisms in the tumor microenvironment
Munn, D. H., & Bronte, V. (2015) · Current Opinion in Immunology · doi:10.1016/j.coi.2015.10.009 · Cited by 519 · see citing works
Prognostic and predictive value of PDL1 expression in breast cancer
Sabatier, R., Finetti, P., Mamessier, É., Adélaı̈de, J., Chaffanet, M., Ali, H. R., Viens, P., Caldas, C., Birnbaum, D., & Bertucci, F. (2014) · Oncotarget · doi:10.18632/oncotarget.3216 · Cited by 506 · see citing works
Ott, P. A., Bang, Y., Berton-Rigaud, D., Élez, E., Pishvaian, M. J., Rugo, H. S., Puzanov, I. J., Mehnert, J. M., Aung, K. L., Lopez, J. S., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2017.72.5952 · Cited by 509 · see citing works
Type I Interferon in Chronic Virus Infection and Cancer
Snell, L. M., McGaha, T. L., & Brooks, D. G. (2017) · Trends in Immunology · doi:10.1016/j.it.2017.05.005 · Cited by 490 · see citing works
Targeting the microenvironment in solid tumors
Belli, C., Trapani, D., Viale, G., D’Amico, P., Duso, B. A., Vigna, P. D., Orsi, F., & Curigliano, G. (2018) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2018.02.004 · Cited by 506 · see citing works
Kwok, G. W., Yau, T. C. C., Chiu, J. W. Y., Tse, E., & Kwong, Y. (2016) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2016.1199310 · Cited by 509 · see citing works
Targeting the IDO1/TDO2–KYN–AhR Pathway for Cancer Immunotherapy – Challenges and Opportunities
Cheong, J. E., & Sun, L. (2017) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2017.11.007 · Cited by 489 · see citing works
Reversing T-cell Dysfunction and Exhaustion in Cancer
Zarour, H. M. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-1849 · Cited by 462 · see citing works
The Next Hurdle in Cancer Immunotherapy: Overcoming the Non–T-Cell–Inflamed Tumor Microenvironment
Gajewski, T. F. (2015) · Seminars in Oncology · doi:10.1053/j.seminoncol.2015.05.011 · Cited by 485 · see citing works
Winograd, R., Byrne, K. T., Evans, R. A., Odorizzi, P. M., Meyer, A. R. L., Bajor, D. L., Clendenin, C., Stanger, B. Z., Furth, E. E., Wherry, E. J., et al. (2015) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-14-0215 · Cited by 459 · see citing works
Thompson, E. D., ZAHURAK, M. L., Murphy, A. G., Cornish, T. C., Cuka, N. S., Abdelfatah, E., Yang, S. C., Duncan, M. D., Ahuja, N., Taube, J. M., et al. (2016) · Gut · doi:10.1136/gutjnl-2015-310839 · Cited by 477 · see citing works
Acquired resistance to immunotherapy and future challenges
Restifo, N. P., Smyth, M. J., & Snyder, A. (2016) · Nature reviews. Cancer · doi:10.1038/nrc.2016.2 · Cited by 463 · see citing works
Wu, M., Huang, Q., Xie, Y., Wu, X., Ma, H., Zhang, Y., & Xia, Y. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01242-2 · Cited by 471 · see citing works
Schalper, K. A., Velcheti, V., Carvajal, D. E., Wimberly, H., Brown, J. R., Pusztai, L., & Rimm, D. L. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-2702 · Cited by 449 · see citing works
Spatially distinct tumor immune microenvironments stratify triple-negative breast cancers
Gruosso, T., Gigoux, M., Manem, V. S., Bertos, N., Zuo, D., Perlitch, I., Saleh, S. M. I., Zhao, H., Souleimanova, M., Johnson, R. M., et al. (2019) · Journal of Clinical Investigation · doi:10.1172/jci96313 · Cited by 445 · see citing works
The Role of Myeloid-Derived Suppressor Cells (MDSC) in Cancer Progression
Umansky, V., Blattner, C., Gebhardt, C., & Utikal, J. S. (2016) · Vaccines · doi:10.3390/vaccines4040036 · Cited by 440 · see citing works
Lou, Y., Diao, L., Parra, E. R., Denning, W. L., Chen, L., Fan, Y. H., Byers, L. A., Wang, J., Papadimitrakopoulou, V. A., Behrens, C., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-1434 · Cited by 439 · see citing works
PD-L1 Expression in Lung Cancer
Yu, H., Boyle, T. A., Zhou, C., Rimm, D. L., & Hirsch, F. R. (2016) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2016.04.014 · Cited by 482 · see citing works
Small molecule inhibitors targeting the PD-1/PD-L1 signaling pathway
Wu, Q., Li, J., Li, S., He, Q., Yang, B., & Cao, J. (2020) · Acta Pharmacologica Sinica · doi:10.1038/s41401-020-0366-x · Cited by 425 · see citing works
Labadie, B. W., Bao, R., & Luke, J. J. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-2882 · Cited by 413 · see citing works
CD39 Expression Defines Cell Exhaustion in Tumor-Infiltrating CD8+ T Cells
Canale, F. P., Ramello, M. C., Núñez, N. G., Furlan, C. L. A., Bossio, S., Serrán, M. G., Tosello, J., del Castillo, A., Ledesma, M., Sedlik, C., et al. (2017) · Cancer Research · doi:10.1158/0008-5472.can-16-2684 · Cited by 401 · see citing works
- 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.
- Venue
- Science Translational Medicine
- Published
- 2013-08-28
- Volume
- 5
- Issue
- 200
- Pages
- 200ra116-200ra116
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- 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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