Roles of PD-1/PD-L1 Pathway: Signaling, Cancer, and Beyond

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

PD-1 Blockade in Tumors with Mismatch-Repair Deficiency

Le, D. T., Uram, J. N., Wang, H., Bartlett, B. R., Kemberling, H., Eyring, A. D., Skora, A. D., Luber, B. S., Azad, N. S., Laheru, D., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1500596 · Cited by 9,377

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

Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer

Rizvi, N. A., Hellmann, M. D., Snyder, A., Kvistborg, P., Makarov, V., Havel, J. J., Lee, W., Yuan, J., Wong, P., Ho, T. S., et al. (2015) · Science · doi:10.1126/science.aaa1348 · Cited by 7,802

Cancer immunotherapy using checkpoint blockade

Ribas, A., & Wolchok, J. D. (2018) · Science · doi:10.1126/science.aar4060 · Cited by 6,791

Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade

Le, D. T., Durham, J. N., Smith, K. N., Wang, H., Bartlett, B. R., Aulakh, L. K., Lu, S., Kemberling, H., Wilt, C., Luber, B. S., et al. (2017) · Science · doi:10.1126/science.aan6733 · Cited by 6,645

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

Comprehensive molecular characterization of gastric adenocarcinoma

The Cancer Genome Atlas Research Network (2014) · Nature · doi:10.1038/nature13480 · Cited by 6,498

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

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

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

The immune contexture in human tumours: impact on clinical outcome

Fridman, W. H., Pagès, F., Sautès-Fridman, C., & Galon, J. (2012) · Nature reviews. Cancer · doi:10.1038/nrc3245 · Cited by 4,981

Nivolumab plus Ipilimumab in Advanced Melanoma

Wolchok, J. D., Kluger, H., Callahan, M. K., Postow, M. A., Rizvi, N. A., Lesokhin, A. M., Segal, N. H., Ariyan, C. E., Gordon, R.-A., Reed, K., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1302369 · Cited by 4,230

Molecular 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

Metabolic Competition in the Tumor Microenvironment Is a Driver of Cancer Progression

Chang, C.-H., Qiu, J., O’Sullivan, D., Buck, M. D., Noguchi, T., Curtis, J. D., Chen, Q., Gindin, M., Gubin, M. M., van der Windt, G. J. W., et al. (2015) · Cell · doi:10.1016/j.cell.2015.08.016 · Cited by 3,331

PD-L2 is a second ligand for PD-1 and inhibits T cell activation

Latchman, Y., Wood, C. R., Chernova, T., Chaudhary, D., Borde, M., Chernova, I., Iwai, Y., Long, A. J., Brown, J. A., Nunes, R., et al. (2001) · Nature Immunology · doi:10.1038/85330 · Cited by 2,955

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

Exploiting tumour hypoxia in cancer treatment

Brown, J. M., & Wilson, W. R. (2004) · Nature Reviews Cancer · doi:10.1038/nrc1367 · Cited by 2,828

Development of Lupus-like Autoimmune Diseases by Disruption of the PD-1 Gene Encoding an ITIM Motif-Carrying Immunoreceptor

Nishimura, H., Nose, M., Hiai, H., Minato, N., & Honjo, T. (1999) · Immunity · doi:10.1016/s1074-7613(00)80089-8 · Cited by 2,749

PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression

Day, C. L., Kaufmann, D. E., Kiepiela, P., Brown, J. A., Moodley, E. S., Reddy, S., Mackey, E. W., Miller, J. D., Leslie, A. J., DePierres, C., et al. (2006) · Nature · doi:10.1038/nature05115 · Cited by 2,680

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

Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab

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

PD-L1 is a novel direct target of HIF-1α, and its blockade under hypoxia enhanced: MDSC-mediated T cell activation

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

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

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

Immunological effects of conventional chemotherapy and targeted anticancer agents

Galluzzi, L., Buqué, A., Kepp, O., Zitvogel, L., & Kroemer, G. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.10.012 · Cited by 1,530

MYC regulates the antitumor immune response through CD47 and PD-L1

Casey, S. C., Tong, L., Li, Y., Do, R., Walz, S., Fitzgerald, K. N., Gouw, A. M., Baylot, V., Gütgemann, I., Eilers, M., et al. (2016) · Science · doi:10.1126/science.aac9935 · Cited by 1,403

Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity

Curiel, T. J., Wei, S., Dong, H., Alvarez, X., Cheng, P., Mottram, P., Krzysiek, R., Knutson, K. L., Daniel, B., Zimmermann, M. C., et al. (2003) · Nature Medicine · doi:10.1038/nm863 · Cited by 1,314

PD-1 and PD-1 ligands: from discovery to clinical application

Okazaki, T., & Honjo, T. (2007) · International Immunology · doi:10.1093/intimm/dxm057 · Cited by 1,310

Epigenetic silencing of TH1-type chemokines shapes tumour immunity and immunotherapy

Peng, D., Kryczek, I., Nagarsheth, N., Zhao, L., Wei, S., Wang, W., Sun, Y., Zhao, E., Vatan, L., Szeliga, W., et al. (2015) · Nature · doi:10.1038/nature15520 · Cited by 1,201

Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2

Yokosuka, T., Takamatsu, M., Kobayashi-Imanishi, W., Hashimoto-Tane, A., Azuma, M., & Saito, T. (2012) · Journal of Experimental Medicine · doi:10.1084/jem.20112741 · Cited by 1,161

Rescue of exhausted CD8 T cells by PD-1–targeted therapies is CD28-dependent

Kamphorst, A. O., Wieland, A., Nasti, T., Yang, S., Zhang, R., Barber, D. L., Konieczny, B. T., Daugherty, C. Z., Koenig, L., Yu, K., et al. (2017) · Science · doi:10.1126/science.aaf0683 · Cited by 1,015

Cyclin D–CDK4 kinase destabilizes PD-L1 via cullin 3–SPOP to control cancer immune surveillance

Zhang, J., Bu, X., Wang, H., Zhu, Y., Geng, Y., Nihira, N. T., Tan, Y., Ci, Y., Wu, F., Dai, X., et al. (2018) · Nature · doi:10.1038/nature25015 · Cited by 1,013

The Tumor Microenvironment Represses T Cell Mitochondrial Biogenesis to Drive Intratumoral T Cell Metabolic Insufficiency and Dysfunction

Scharping, N. E., Menk, A. V., Moreci, R. S., Whetstone, R. D., Dadey, R. E., Watkins, S. C., Ferris, R. L., & Delgoffe, G. M. (2016) · Immunity · doi:10.1016/j.immuni.2016.07.009 · Cited by 848

The PD-1/PD-L1 axis modulates the natural killer cell versus multiple myeloma effect: a therapeutic target for CT-011, a novel monoclonal anti–PD-1 antibody

Benson, D. M., Bakan, C. E., Mishra, A., Hofmeister, C. C., Efebera, Y., Becknell, B., Baiocchi, R. A., Zhang, J., Yu, J., Smith, M. K., et al. (2010) · Blood · doi:10.1182/blood-2010-02-271874 · Cited by 807

Control of PD-L1 Expression by Oncogenic Activation of the AKT-mTOR Pathway in Non-Small Cell Lung Cancer.

Lastwika, K. J., Wilson, W., Li, Q. K., Norris, J., Xu, H., Ghazarian, S. R., Kitagawa, H., Kawabata, S., Taube, J. M., Yao, S., et al. (2016) · Cancer Research · doi:10.1158/0008-5472.can-14-3362 · Cited by 785

PD-1 signaling in primary T cells

Riley, J. L. (2009) · Immunological Reviews · doi:10.1111/j.1600-065x.2009.00767.x · Cited by 778

Costimulatory B7-H1 in renal cell carcinoma patients: Indicator of tumor aggressiveness and potential therapeutic target

Thompson, R. H., Gillett, M. D., Cheville, J. C., Lohse, C. M., Dong, H., Webster, W. S., Krejci, K. G., Lobo, J. R., Sengupta, S., Chen, L., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0406351101 · Cited by 776

A mechanism of hypoxia-mediated escape from adaptive immunity in cancer cells

Barsoum, I. B., Smallwood, C. A., Siemens, D. R., & Graham, C. H. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-0992 · Cited by 767

Identification of CMTM6 and CMTM4 as PD-L1 protein regulators

Mezzadra, R., Sun, C., Jae, L. T., Gomez-Eerland, R., de Vries, E., Wu, W., Logtenberg, M. E. W., Slagter, M., Rozeman, E. A., Hofland, I., et al. (2017) · Nature · doi:10.1038/nature23669 · Cited by 697

Autoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice

Okazaki, T., Tanaka, Y., Nishio, R., Mitsuiye, T., Mizoguchi, A., Wang, J., Ishida, M., Hiai, H., Matsumori, A., Minato, N., et al. (2003) · Nature Medicine · doi:10.1038/nm955 · Cited by 689

PDL1 Regulation by p53 via miR-34

Cortez, M. A., Ivan, C., Valdecanas, D., Wang, X., Peltier, H. J., Ye, Y., Araujo, L., Carbone, D. P., Shilo, K., Giri, D. K., et al. (2016) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/djv303 · Cited by 683

Restriction of PD-1 function by cis -PD-L1/CD80 interactions is required for optimal T cell responses

Sugiura, D., Maruhashi, T., Okazaki, I.-M., Shimizu, K., Maeda, T. K., Takemoto, T., & Okazaki, T. (2019) · Science · doi:10.1126/science.aav7062 · Cited by 386

IL-18 Induces PD-1–Dependent Immunosuppression in Cancer

Terme, M., Ullrich, E., Aymeric, L., Meinhardt, K., Desbois, M., Delahaye, N., Viaud, S., Ryffel, B., Yagita, H., Kaplanski, G., et al. (2011) · Cancer Research · doi:10.1158/0008-5472.can-11-0993 · Cited by 376

FBXO38 mediates PD-1 ubiquitination and regulates anti-tumour immunity of T cells

Meng, X., Liu, X., Guo, X., Jiang, S., Chen, T., Hu, Z., Liu, H., Bai, Y., Xue, M., Hu, R., et al. (2018) · Nature · doi:10.1038/s41586-018-0756-0 · Cited by 303

Expression and regulation of the PD-L1 immunoinhibitory molecule on microvascular endothelial cells

Eppihimer, M., Gunn, J., Freeman, G., Greenfield, E., Chernova, T., Erickson, J., & Leonard, J. (2002) · Microcirculation · doi:10.1080/713774061 · Cited by 272

PTEN Loss Increases PD-L1 Protein Expression and Affects the Correlation between PD-L1 Expression and Clinical Parameters in Colorectal Cancer

Song, M., Chen, D., Lu, B., Wang, C., Zhang, J., Huang, L., Wang, X., Timmons, C. L., Hu, J., Liu, B., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0065821 · Cited by 266

Association of a putative regulatory polymorphism in the PD‐1 gene with susceptibility to type 1 diabetes

Nielsen, C., Hansen, D., Husby, S., Jacobsen, B. B., & Lillevang, S. T. (2003) · Tissue Antigens · doi:10.1046/j.1399-0039.2003.00136.x · Cited by 232

Renal cell carcinoma programmed death-ligand 1, a new direct target of hypoxia-inducible factor-2 alpha, is regulated by von Hippel–Lindau gene mutation status

Messai, Y., Gad, S., Noman, M. Z., Le Teuff, G., Couve, S., Janji, B., Kammerer, S. F., Rioux-Leclerc, N., Hasmim, M., Ferlicot, S., et al. (2016) · European Urology · doi:10.1016/j.eururo.2015.11.029 · Cited by 168

PD-1 and PD-L1: architects of immune symphony and immunotherapy breakthroughs in cancer treatment

Parvez, A., Choudhary, F., Mudgal, P., Khan, R., Qureshi, K. A., Farooqi, H., & Aspatwar, A. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1296341 · Cited by 216

Exosomal PD‐L1: New Insights Into Tumor Immune Escape Mechanisms and Therapeutic Strategies

Zhou, K., Guo, S., Li, F., Sun, Q., & Liang, G. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.569219 · Cited by 99

Phase-Transformation Nanoparticle-Mediated Sonodynamic Therapy: An Effective Modality to Enhance Anti-Tumor Immune Response by Inducing Immunogenic Cell Death in Breast Cancer

Si, Y., Yue, J., Liu, Z., Li, M., Du, F., Wang, X., Dai, Z., Hu, N., Ju, J., Gao, S., et al. (2021) · International Journal of Nanomedicine · doi:10.2147/ijn.s297933 · Cited by 52

SHR-2005, an FcγR-Dependent CD40 Agonistic Antibody with Potent Antitumor Activities and Favorable Safety Profile

Wang, L.-M., Yang, C., Sun, X., Tian, Y., Zhang, J., Wang, X., Zhou, L., Wang, Z., Lin, Y., Wu, T., et al. (2025) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-24-0999 · Cited by 2