Safety and activity of anti-PD-L1 antibody in patients with advanced cancer
Open accessAbstract
BACKGROUND: Programmed death 1 (PD-1) protein, a T-cell coinhibitory receptor, and one of its ligands, PD-L1, play a pivotal role in the ability of tumor cells to evade the host's immune system. Blockade of interactions between PD-1 and PD-L1 enhances immune function in vitro and mediates antitumor activity in preclinical models. METHODS: In this multicenter phase 1 trial, we administered intravenous anti-PD-L1 antibody (at escalating doses ranging from 0.3 to 10 mg per kilogram of body weight) to patients with selected advanced cancers. Anti-PD-L1 antibody was administered every 14 days in 6-week cycles for up to 16 cycles or until the patient had a complete response or confirmed disease progression. RESULTS: As of February 24, 2012, a total of 207 patients--75 with non-small-cell lung cancer, 55 with melanoma, 18 with colorectal cancer, 17 with renal-cell cancer, 17 with ovarian cancer, 14 with pancreatic cancer, 7 with gastric cancer, and 4 with breast cancer--had received anti-PD-L1 antibody. The median duration of therapy was 12 weeks (range, 2 to 111). Grade 3 or 4 toxic effects that investigators considered to be related to treatment occurred in 9% of patients. Among patients with a response that could be evaluated, an objective response (a complete or partial response) was observed in 9 of 52 patients with melanoma, 2 of 17 with renal-cell cancer, 5 of 49 with non-small-cell lung cancer, and 1 of 17 with ovarian cancer. Responses lasted for 1 year or more in 8 of 16 patients with at least 1 year of follow-up. CONCLUSIONS: Antibody-mediated blockade of PD-L1 induced durable tumor regression (objective response rate of 6 to 17%) and prolonged stabilization of disease (rates of 12 to 41% at 24 weeks) in patients with advanced cancers, including non-small-cell lung cancer, melanoma, and renal-cell cancer. (Funded by Bristol-Myers Squibb and others; ClinicalTrials.gov number, NCT00729664.).
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
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?
In PDAC, where several immune defects coexist, pairing two standard immune checkpoint inhibitors to boost effector T cells has little or no effect.
“For example, it is now evident that simply combining two “off the shelf” immune checkpoint inhibitors to enhance effector T cell function – a strategy that has worked in several other solid cancers – has minimal to no impact in a disease where a multiplicity of immune defects co-exist283,284.”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [283]
Clinical blockade of B7-H1/PD-1 may rescue T cell effector functions in vivo and results in significant objective clinical responses.
“A promising aspect is that clinical blockade of B7-H1/PD-1, the key T cell exhaustion pathway, may rescue T cell effector functions in vivo, and results in significant objective clinical responses [32,33].”
From T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment (2013) · cites this paper as [32]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
New Guidelines to Evaluate the Response to Treatment in Solid Tumors
Therasse, P., Arbuck, S. G., Eisenhauer, E. A., Wanders, J., Kaplan, R. S., Rubinstein, L., Verweij, J., Van Glabbeke, M., van Oosterom, A. T., Christian, M. C., et al. (2000) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/92.3.205 · Cited by 15,660 · see citing works
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 7× · see citing works
“All squamous type All doses 13 1 8 (0-36) ND 3 23 (5-54) 43 (15-71)”
InfluentialThe blockade of immune checkpoints in cancer immunotherapy
Pardoll, D. M. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3239 · Cited by 13,838 · cited 6× · see citing works
“All patients All doses 49 5 10 (3-22) 6 12 (5-25) 31 (17-45)”
InfluentialSelf-citationSafety, 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 · cited 6× · see citing works
“All squamous type All doses 13 1 8 (0-36) ND 3 23 (5-54) 43 (15-71)”
InfluentialSelf-citationToxicity and response criteria of the Eastern Cooperative Oncology Group
Oken, M. M., Creech, R. H., Tormey, D. C., Horton, J., Davis, T. E., Mcfadden, E. T., & Carbone, P. P. (1982) · American Journal of Clinical Oncology · doi:10.1097/00000421-198212000-00014 · Cited by 11,607 · cited 5× · see citing works
“All patients All doses 49 5 10 (3-22) 6 12 (5-25) 31 (17-45)”
InfluentialFreeman, 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 · see citing works
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 · see citing works
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 · cited 7× · see citing works
“All squamous type All doses 13 1 8 (0-36) ND 3 23 (5-54) 43 (15-71)”
InfluentialCancer immunotherapy comes of age
Mellman, I., Coukos, G., & Dranoff, G. (2011) · Nature · doi:10.1038/nature10673 · Cited by 3,893 · cited 5× · see citing works
“All patients All doses 49 5 10 (3-22) 6 12 (5-25) 31 (17-45)”
InfluentialWolchok, J. D., Hoos, A., O'Day, S. J., Weber, J. S., Hamid, O., Lebbé, C., Maio, M., Binder, M., Bohnsack, O., Nichol, G. M., et al. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-1624 · Cited by 3,214 · cited 6× · see citing works
“All squamous type All doses 13 1 8 (0-36) ND 3 23 (5-54) 43 (15-71)”
InfluentialSelf-citationIwai, Y., Ishida, M., Tanaka, Y., Okazaki, T., Honjo, T., & Minato, N. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.192461099 · Cited by 3,204 · cited 5× · see citing works
“All patients All doses 49 5 10 (3-22) 6 12 (5-25) 31 (17-45)”
InfluentialBrahmer, 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 6× · see citing works
“All squamous type All doses 13 1 8 (0-36) ND 3 23 (5-54) 43 (15-71)”
InfluentialSelf-citationPD-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 · cited 6× · see citing works
“All squamous type All doses 13 1 8 (0-36) ND 3 23 (5-54) 43 (15-71)”
InfluentialTivol, E. A., Borriello, F., Schweitzer, A. N., Lynch, W. P., Bluestone, J. A., & Sharpe, A. H. (1995) · Immunity · doi:10.1016/1074-7613(95)90125-6 · Cited by 2,914 · cited 7× · see citing works
“All squamous type All doses 13 1 8 (0-36) ND 3 23 (5-54) 43 (15-71)”
InfluentialNishimura, H., Nose, M., Hiai, H., Minato, N., & Honjo, T. (1999) · Immunity · doi:10.1016/s1074-7613(00)80089-8 · Cited by 2,749 · cited 7× · see citing works
“All squamous type All doses 13 1 8 (0-36) ND 3 23 (5-54) 43 (15-71)”
InfluentialDong, H., Zhu, G., Tamada, K., & Chen, L. (1999) · Nature Medicine · doi:10.1038/70932 · Cited by 2,496 · cited 7× · see citing works
“All squamous type All doses 13 1 8 (0-36) ND 3 23 (5-54) 43 (15-71)”
InfluentialTaube, 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 5× · see citing works
“All patients All doses 49 5 10 (3-22) 6 12 (5-25) 31 (17-45)”
InfluentialSelf-citationButte, M. J., Keir, M. E., Phamduy, T. B., Sharpe, A. H., & Freeman, G. J. (2007) · Immunity · doi:10.1016/j.immuni.2007.05.016 · Cited by 1,733 · cited 6× · see citing works
“All squamous type All doses 13 1 8 (0-36) ND 3 23 (5-54) 43 (15-71)”
InfluentialCTLA-4 is a second receptor for the B cell activation antigen B7.
Linsley, P. S., Brady, W., Urnes, M., Grosmaire, L. S., Damle, N. K., & Ledbetter, J. A. (1991) · The Journal of experimental medicine · doi:10.1084/jem.174.3.561 · Cited by 1,685 · cited 7× · see citing works
“All squamous type All doses 13 1 8 (0-36) ND 3 23 (5-54) 43 (15-71)”
InfluentialInhibitory B7-family molecules in the tumour microenvironment
Zou, W., & Chen, L. (2008) · Nature Reviews Immunology · doi:10.1038/nri2326 · Cited by 1,608 · cited 5× · see citing works
“All patients All doses 49 5 10 (3-22) 6 12 (5-25) 31 (17-45)”
InfluentialPhan, G. Q., Yang, J. C., Sherry, R. M., Hwu, P., Topalian, S. L., Schwartzentruber, D. J., Restifo, N. P., Haworth, L. R., Seipp, C. A., Freezer, L. J., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1533209100 · Cited by 1,575 · cited 7× · see citing works
“All squamous type All doses 13 1 8 (0-36) ND 3 23 (5-54) 43 (15-71)”
InfluentialSelf-citationBlockade 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 · cited 5× · see citing works
“All patients All doses 49 5 10 (3-22) 6 12 (5-25) 31 (17-45)”
InfluentialPD-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 · cited 7× · see citing works
“All squamous type All doses 13 1 8 (0-36) ND 3 23 (5-54) 43 (15-71)”
InfluentialMonoclonal antibodies: versatile platforms for cancer immunotherapy
Weiner, L. M., Surana, R., & Wang, S. (2010) · Nature reviews. Immunology · doi:10.1038/nri2744 · Cited by 1,282 · cited 1× · see citing works
“Squamous subtype 3 4 0 0 (0-60) NA 1 25 (0-81) 50 (1-99)”
B7-Dc, a New Dendritic Cell Molecule with Potent Costimulatory Properties for T Cells
Tseng, S.-Y., Otsuji, M., Gorski, K. S., Huang, X., Slansky, J. E., Pai, S. I., Shalabi, A., Shin, T., Pardoll, D. M., & Tsuchiya, H. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.193.7.839 · Cited by 867 · cited 7× · see citing works
“All squamous type All doses 13 1 8 (0-36) ND 3 23 (5-54) 43 (15-71)”
InfluentialSelf-citationBeck, K. E., Blansfield, J. A., Tran, K. Q., Feldman, A. L., Hughes, M. S., Royal, R. E., Kammula, U. S., Topalian, S. L., Sherry, R. M., Kleiner, D., et al. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2005.04.5716 · Cited by 833 · see citing works
Self-citationInteractions between PD-1 and PD-L1 promote tolerance by blocking the TCR–induced stop signal
Fife, B. T., Pauken, K. E., Eagar, T. N., Kangas, T. O., Wu, J. Q., Tang, Q., Azuma, M., Krummel, M. F., & Bluestone, J. A. (2009) · Nature Immunology · doi:10.1038/ni.1790 · Cited by 759 · see citing works
Hino, R., Kabashima, K., Kato, Y., Yagi, H., Nakamura, M., Honjo, T., Okazaki, T., & TOKURA, Y. (2010) · Cancer · doi:10.1002/cncr.24899 · Cited by 668 · cited 5× · see citing works
“All patients All doses 49 5 10 (3-22) 6 12 (5-25) 31 (17-45)”
InfluentialNovel cancer immunotherapy agents with survival benefit: recent successes and next steps
Sharma, P., Wagner, K., Wolchok, J. D., & Allison, J. P. (2011) · Nature reviews. Cancer · doi:10.1038/nrc3153 · Cited by 639 · cited 6× · see citing works
“All squamous type All doses 13 1 8 (0-36) ND 3 23 (5-54) 43 (15-71)”
InfluentialCancer Immunotherapy Comes of Age
Topalian, S. L., Weiner, G. J., & Pardoll, D. M. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2011.38.0899 · Cited by 591 · see citing works
Self-citationRibas, A., Camacho, L. H., Lopez-Berestein, G., Pavlov, D., Bulanhagui, C. A., Millham, R., Comin-Anduix, B., Reuben, J. M., Seja, E., Parker, C. A., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.01.109 · Cited by 591 · cited 5× · see citing works
“All patients All doses 49 5 10 (3-22) 6 12 (5-25) 31 (17-45)”
InfluentialSelf-citationErratum: Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion
Dong, H., Strome, S. E., Salomão, 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/nm0902-1039c · Cited by 545 · see citing works
B7-H1 Determines Accumulation and Deletion of Intrahepatic CD8+ T Lymphocytes
Dong, H., Zhu, G., Tamada, K., Flies, D. B., van Deursen, J. M. A., & Chen, L. (2004) · Immunity · doi:10.1016/s1074-7613(04)00050-0 · Cited by 370 · cited 5× · see citing works
“All patients All doses 49 5 10 (3-22) 6 12 (5-25) 31 (17-45)”
InfluentialB7-H1/CD80 interaction is required for the induction and maintenance of peripheral T-cell tolerance
Park, J., Omiya, R., Matsumura, Y., Sakoda, Y., Kuramasu, A., Augustine, M. M., Yao, S., Tsushima, F., Narazaki, H., Anand, S., et al. (2010) · Blood · doi:10.1182/blood-2010-01-265975 · Cited by 331 · cited 6× · see citing works
“All squamous type All doses 13 1 8 (0-36) ND 3 23 (5-54) 43 (15-71)”
InfluentialGajewski, T. F., Louahed, J., & Brichard, V. G. (2010) · The Cancer Journal · doi:10.1097/ppo.0b013e3181eacbd8 · Cited by 250 · see citing works
Interaction of human PD-L1 and B7-1
Butte, M. J., Peña‐Cruz, V., Kim, M., Freeman, G. J., & Sharpe, A. H. (2008) · Molecular Immunology · doi:10.1016/j.molimm.2008.05.014 · Cited by 229 · cited 6× · see citing works
“All squamous type All doses 13 1 8 (0-36) ND 3 23 (5-54) 43 (15-71)”
InfluentialThe Programmed Death-1 Ligand 1:B7-1 Pathway Restrains Diabetogenic Effector T Cells In Vivo
Paterson, A. M., Brown, K. E., Keir, M. E., Vanguri, V. K., Riella, L. V., Chandraker, A. K., Sayegh, M. H., Blazar, B. R., Freeman, G. J., & Sharpe, A. H. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1003496 · Cited by 202 · cited 6× · see citing works
“All squamous type All doses 13 1 8 (0-36) ND 3 23 (5-54) 43 (15-71)”
InfluentialYang, J., Riella, L. V., Chock, S., Liu, T., Zhao, X., Yuan, X., Paterson, A. M., Watanabe, T., Vanguri, V. K., Yagita∥, H., et al. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100056 · Cited by 134 · cited 6× · see citing works
“All squamous type All doses 13 1 8 (0-36) ND 3 23 (5-54) 43 (15-71)”
InfluentialImmunotherapy as a strategy for the treatment of non-small-cell lung cancer
Holt, G. E., Podack, E. R., & Raez, L. E. (2010) · Therapy · doi:10.2217/thy.10.84 · Cited by 57 · see citing works
Flagged first, then by citations
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 · see citing works
Haugen, B. R., Alexander, E. K., Bible, K. C., Doherty, G. M., Mandel, S. J., Nikiforov, Y. E., Pacini, F., Randolph, G. W., Sawka, A. M., Schlumberger, M., et al. (2016) · Thyroid® · doi:10.1089/thy.2015.0020 · Cited by 16,535 · 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
Self-citationPD-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 · see citing works
Self-citationPD-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
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 · see citing works
Self-citationDissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq
Tirosh, I., Izar, B., Prakadan, S. M., Wadsworth, M. H., Treacy, D., Trombetta, J. J., Rotem, A., Rodman, C., Lian, C., Murphy, G., et al. (2016) · Science · doi:10.1126/science.aad0501 · Cited by 4,944 · 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
Self-citationElements 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
The future of immune checkpoint therapy
Sharma, P., & Allison, J. P. (2015) · Science · doi:10.1126/science.aaa8172 · Cited by 4,878 · 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
Self-citationInnate 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
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 · see citing works
Self-citationPD-1 Blockade with Nivolumab in Relapsed or Refractory Hodgkin's Lymphoma
Ansell, S. M., Lesokhin, A. M., Borrello, I., Halwani, A. S., Scott, E. C., Gutierrez, M. E., Schuster, S. J., Millenson, M. M., Cattry, D., Freeman, G. J., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1411087 · Cited by 3,564 · see citing works
Self-citationMetabolic 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 · see citing works
Tumor mutational burden and response rate to PD-1 inhibition
Yarchoan, M., Hopkins, A., & Jaffee, E. M. (2017) · New England Journal of Medicine · doi:10.1056/nejmc1713444 · Cited by 3,230 · see citing works
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 3,373 · see citing works
Self-citationGenomic classification of cutaneous melanoma
Akbani, R., Akdemir, K. C., Aksoy, B. A., Albert, M., Ally, A., Amin, S. B., Arachchi, H., Arora, A., Auman, J. T., Ayala, B., et al. (2015) · Cell · doi:10.1016/j.cell.2015.05.044 · Cited by 3,151 · see citing works
Zhang, Y., & Zhang, Z. (2020) · Cellular and Molecular Immunology · doi:10.1038/s41423-020-0488-6 · Cited by 2,815 · see citing works
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 · see citing works
Self-citationImmune Checkpoint Blockade in Cancer Therapy
Postow, M. A., Callahan, M. K., & Wolchok, J. D. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2014.59.4358 · Cited by 2,736 · see citing works
Weber, J. S., D’Angelo, S. P., Minor, D. R., Hodi, F. S., Gutzmer, R., Neyns, B., Höeller, C., Khushalani, N. I., Miller, W. H., Lao, C. D., et al. (2015) · The Lancet Oncology · doi:10.1016/s1470-2045(15)70076-8 · Cited by 2,676 · see citing works
Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma
Andtbacka, R. H. I., Kaufman, H. L., Collichio, F. A., AMATRUDA, T. T., Senzer, N. N., Chesney, J. A., Delman, K. A., S̄pitler, L. E., Puzanov, I. J., Agarwala, S. S., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2014.58.3377 · Cited by 2,646 · see citing works
Comprehensive Characterization of Cancer Driver Genes and Mutations
Bailey, M. H., Tokheim, C., Porta-Pardo, E., Sengupta, S., Bertrand, D., Weerasinghe, A., Colaprico, A., Wendl, M. C., Kim, J., Reardon, B., et al. (2018) · Cell · doi:10.1016/j.cell.2018.02.060 · Cited by 2,316 · see citing works
“MSI cases show improved response to immune checkpoint therapy, independent of histology (Brahmer et al., 2012; Gryfe et al., 2000; Le et al., 2015).”
BackgroundT cell exclusion, immune privilege, and the tumor microenvironment
Joyce, J. A., & Fearon, D. T. (2015) · Science · doi:10.1126/science.aaa6204 · Cited by 2,494 · see citing works
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 · see citing works
Zou, W., Wolchok, J. D., & Chen, L. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aad7118 · Cited by 2,382 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Self-citationImmune-related adverse events with immune checkpoint blockade: a comprehensive review
Michot, J. M., Bigenwald, C., Champiat, S., Collins, M., Carbonnel, F., Postel-Vinay, S., Berdelou, A., Varga, A., Bahleda, R., Hollebecque, A., et al. (2016) · European Journal of Cancer · doi:10.1016/j.ejca.2015.11.016 · Cited by 2,127 · see citing works
“IRAEs are frequent; they occur in up to 90% of patients treated with an anti-CTLA-4 antibody [2] and 70% of patients treated with an PD-1/PD-L1 antibody [11,17].”
BackgroundNoman, 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 · see citing works
Feig, C., Jones, J. O., Kraman, M., Wells, R. J. B., Deonarine, A., Chan, D. S., Connell, C. M., Roberts, E. W., Zhao, Q., Caballero, O. L., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1320318110 · Cited by 2,100 · 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
Immunotherapy in colorectal cancer: Rationale, challenges and potential
Ganesh, K., Stadler, Z. K., Cercek, A., Mendelsohn, R. B., Shia, J., Segal, N. H., & Diaz, L. A. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0126-x · Cited by 1,954 · see citing works
The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy
Havel, J. J., Chowell, D., & Chan, T. A. (2019) · Nature Reviews Cancer · doi:10.1038/s41568-019-0116-x · Cited by 2,286 · see citing works
Taube, J. M., Klein, A., Brahmer, J. R., Xu, H., Pan, X., Kim, J. H., Chen, L., Pardoll, D. M., Topalian, S. L., & Anders, R. A. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-3271 · Cited by 2,324 · see citing works
Self-citationChiappinelli, 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 · see citing works
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 1,980 · see citing works
Non-small-cell lung cancers: a heterogeneous set of diseases
Chen, Z., Brainson, C. F., Hammerman, P. S., Kim, C. F., & Wong, K. (2014) · Nature reviews. Cancer · doi:10.1038/nrc3775 · Cited by 1,935 · see citing works
Cancer-related inflammation and treatment effectiveness
Diakos, C. I., Charles, K. A., McMillan, D. C., & Clarke, S. J. (2014) · The Lancet Oncology · doi:10.1016/s1470-2045(14)70263-3 · Cited by 2,193 · see citing works
Global characterization of T cells in non-small-cell lung cancer by single-cell sequencing
Guo, X., Zhang, Y., Zheng, L., Zheng, C., Song, J., Zhang, Q., Kang, B., Liu, Z., Jin, L., Xing, R., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0045-3 · Cited by 1,651 · see citing works
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 · see citing works
Self-citationComprehensive review of targeted therapy for colorectal cancer
Xie, Y.-H., Chen, Y.-X., & Fang, J.-Y. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-0116-z · Cited by 1,687 · see citing works
Spranger, S., Spaapen, R. M., Zha, Y., Williams, J., Meng, Y., Ha, T. T., & Gajewski, T. F. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3006504 · Cited by 1,677 · see citing works
Loi, S., Sirtaine, N., Piette, F., Salgado, R., Viale, G., Eenoo, F. V., Rouas, G., Francis, P. A., Crown, J. P., Hitre, E., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2011.41.0902 · Cited by 1,634 · see citing works
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 · see citing works
“Importantly, (1) elevation of TIM-3 expression in T cells was predominantly found on the therapeutic PD-1 antibody-bound subset, (2) upregulation of TIM-3 was only detected in tumour-bearing lungs but not in sentinel lymph nodes and peripheral blood, (3) TIM-3 positivity was significantly correlated with duration of P…”
BackgroundChen, Q., Xu, L., Liang, C., Wang, C., Peng, R., & Liu, Z. (2016) · Nature Communications · doi:10.1038/ncomms13193 · Cited by 1,600 · see citing works
Lei, X., Lei, Y., Li, J.-K., Du, W.-X., Li, R.-G., Yang, J., Li, J., Li, F., & Tan, H.-B. (2020) · Cancer Letters · doi:10.1016/j.canlet.2019.11.009 · Cited by 1,470 · 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
Self-citationRegulatory 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
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
Self-citationMittal, 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 · see citing works
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 · see citing works
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 1,489 · see citing works
Spranger, S., Dai, D., Horton, B., & Gajewski, T. F. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.04.003 · Cited by 1,441 · see citing works
“Immunotherapy has emerged as a potent and effective treatment for multiple cancer types (Brahmer et al., 2012; Hodi et al., 2010; Larkin et al., 2015).”
BackgroundAnti–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
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 1,412 · see citing works
Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy
Mager, L. F., Burkhard, R., Pett, N., Cooke, N. C. A., Brown, K., Ramay, H., Paik, S., Stagg, J., Groves, R. A., Gallo, M., et al. (2020) · Science · doi:10.1126/science.abc3421 · Cited by 1,407 · see citing works
A Paradigm Shift in Cancer Immunotherapy: From Enhancement to Normalization
Sanmamed, M. F., & Chen, L. (2018) · Cell · doi:10.1016/j.cell.2018.09.035 · Cited by 1,394 · 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
Self-citationCancer immunotherapy: harnessing the immune system to battle cancer
Yang, Y. (2015) · Journal of Clinical Investigation · doi:10.1172/jci83871 · Cited by 1,366 · see citing works
Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumours
Galon, J., Mlecnik, B., Bindea, G., Angell, H. K., Berger, A., Lagorce, C., Lugli, A., Zlobec, I., Hartmann, A., Bifulco, C. B., et al. (2013) · The Journal of Pathology · doi:10.1002/path.4287 · Cited by 1,358 · see citing works
Epigenetic Determinants of CancerPreprint
Baylin, S. B., & Jones, P. A. (2016) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a019505 · Cited by 1,363 · see citing works
“These latter include not only standard chemotherapies, but also, intriguingly, an exciting new immunotherapy (Brahmer et al. 2012; Topalian et al. 2012), which targets breaking lymphocyte immune tolerance to render these cells immune competent (Wrangle et al. 2013).”
BackgroundPancreatic cancer: Advances and challenges
Halbrook, C. J., Lyssiotis, C. A., Pasca di Magliano, M., & Maitra, A. (2023) · Cell · doi:10.1016/j.cell.2023.02.014 · Cited by 1,321 · see citing works
Pitt, J. M., Marabelle, A., Eggermont, A. M. M., Soria, J., Kroemer, G., & Zitvogel, L. (2016) · Annals of Oncology · doi:10.1093/annonc/mdw168 · Cited by 1,344 · see citing works
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 · see citing works
“Similarly, blockade of the PD-1/PD-L1 signaling axis is also sufficient to induce significant responses in multiple tumor types (Brahmer et al., 2012; Topalian et al., 2012).”
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
The tumour microenvironment in pancreatic cancer — clinical challenges and opportunities
Ho, W. J., Jaffee, E. M., & Zheng, L. (2020) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-0363-5 · Cited by 1,295 · 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
Translational biology of osteosarcoma
Kansara, M., Teng, M. W., Smyth, M. J., & Thomas, D. M. (2014) · Nature Reviews Cancer · doi:10.1038/nrc3838 · Cited by 1,294 · see citing works
Gong, J., Chehrazi‐Raffle, A., Reddi, S., & Salgia, R. (2018) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-018-0316-z · Cited by 1,279 · see citing works
Activation of the PD-1 Pathway Contributes to Immune Escape in EGFR-Driven Lung Tumors
Akbay, E. A., Koyama, S., Carretero, J., Altabef, A. B., Tchaicha, J. H., Christensen, C. L., Mikse, O. R., Cherniack, A. D., Beauchamp, E. M., Pugh, T. J., et al. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0310 · Cited by 1,237 · see citing works
Cancer immunotherapy: the beginning of the end of cancer?
Farkona, S., Diamandis, E. P., & Blasutig, I. M. (2016) · BMC Medicine · doi:10.1186/s12916-016-0623-5 · Cited by 1,192 · see citing works
“Anti-PD1 and anti-PD-L1 antibodies -Sufficient clinical responses which are often long-lasting -Therapeutic responses in patients within a broad range of human cancers -Reduced toxicity compared to anti-CTLA-4 antibodies -Only a relatively small fraction of patients obtain clinical benefit [2, 84, 90]”
BackgroundHamanishi, J., Mandai, M., Ikeda, T., Minami, M., Kawaguchi, A., Murayama, T., Kanai, M., Mori, Y., Matsumoto, S., Chikuma, S., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2015.62.3397 · Cited by 1,176 · see citing works
Overcoming 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
Melief, C. J. M., van Hall, T., Arens, R., OSSENDORP, F. A., & van der Burg, S. H. (2015) · Journal of Clinical Investigation · doi:10.1172/jci80009 · Cited by 1,182 · see citing works
The future of cancer treatment: immunomodulation, CARs and combination immunotherapy
Khalil, D. N., Smith, E. L., Brentjens, R. J., & Wolchok, J. D. (2016) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2016.25 · Cited by 1,151 · see citing works
Targeting the cancer epigenome for therapy
Jones, P. A., Issa, J. J., & Baylin, S. B. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.93 · Cited by 1,132 · see citing works
Gridelli, C., Rossi, A., Carbone, D. P., Guarize, J., Karachaliou, N., Mok, T. S. K., Petrella, F., Spaggiari, L., & Rosell, R. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.9 · Cited by 1,121 · see citing works
Macrophage Regulation of Tumor Responses to Anticancer Therapies
De Palma, M., & Lewis, C. E. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.02.013 · Cited by 1,079 · see citing works
Towards personalized, tumour-specific, therapeutic vaccines for cancer
Hu, Z., Ott, P. A., & Wu, C. J. (2018) · Nature Reviews Immunology · doi:10.1038/nri.2017.131 · Cited by 1,067 · see citing works
Radiotherapy and immunotherapy: a beneficial liaison?
Weichselbaum, R. R., Liang, H. L., Deng, L., & Fu, Y. (2017) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2016.211 · Cited by 1,073 · see citing works
Cancer cell–autonomous contribution of type I interferon signaling to the efficacy of chemotherapy
Sistigu, A., Yamazaki, T., Vacchelli, E., Chaba, K., Enot, D. P., Adam, J., Vitale, I., Goubar, A., Baracco, E. E., Remédios, C., et al. (2014) · Nature Medicine · doi:10.1038/nm.3708 · Cited by 1,042 · see citing works
Targeting STAT3 in Cancer Immunotherapy
Zou, S., Tong, Q., Liu, B., Huang, W., Tian, Y., & Fu, X. (2020) · Molecular Cancer · doi:10.1186/s12943-020-01258-7 · Cited by 1,075 · see citing works
Targeting neoantigens to augment antitumour immunity
Yarchoan, M., Johnson, B. A., Lutz, E. R., Laheru, D. A., & Jaffee, E. M. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2016.154 · Cited by 997 · 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
“…are approximately 15% (Hodi et al., 2010; Robert et al., 2011); those following targeting of the PD-1-PD-L1 axis rarely exceed 40% (and are often considerably beneath this figure), and there are a large number of partial responders (Brahmer et al., 2012; Hamid et al., 2013; Topalian et al., 2012).”
InfluentialChen, P.-L., Roh, W., Reuben, A., Cooper, Z. A., Spencer, C. N., Prieto, P. A., Miller, J. P., Bassett, R. L., Gopalakrishnan, V., Wani, K., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-1545 · Cited by 988 · see citing works
Self-citationMlecnik, B., Bindea, G., Angell, H. K., Maby, P., Angelova, M., Tougeron, D., Church, S. E., Lafontaine, L., Fischer, M., Fredriksen, T., et al. (2016) · Immunity · doi:10.1016/j.immuni.2016.02.025 · Cited by 1,034 · see citing works
Denkert, C., von Minckwitz, G., Brase, J. C., Sinn, B. V., Gade, S., Kronenwett, R., Pfitzner, B. M., Salat, C., Loi, S., Schmitt, W., et al. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2014.58.1967 · Cited by 1,026 · see citing works
PD-1 + regulatory T cells amplified by PD-1 blockade promote hyperprogression of cancer
Kamada, T., Togashi, Y., Tay, C., Ha, D., Sasaki, A., Nakamura, Y., Sato, E., Fukuoka, S., Tada, Y., Tanaka, A., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1822001116 · Cited by 1,006 · see citing works
Kinase inhibitors: the road ahead
Ferguson, F. M., & Gray, N. S. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.21 · Cited by 1,009 · see citing works
Targeting tumor-associated macrophages to synergize tumor immunotherapy
Xiang, X., Wang, J., Lu, D., & Xu, X. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00484-9 · Cited by 982 · see citing works
Chen, L., Gibbons, D. L., Goswami, S., Cortez, M. A., Ahn, Y., Byers, L. A., Zhang, X., Yi, X., Dwyer, D. W., Lin, W., et al. (2014) · Nature Communications · doi:10.1038/ncomms6241 · Cited by 972 · see citing works
Dong, Z.-Y., Zhong, W.-Z., Zhang, X.-C., Su, J., Xie, Z., Liu, S.-Y., Tu, H.-Y., Chen, H.-J., Sun, Y.-L., Zhou, Q., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-2554 · Cited by 959 · see citing works
Krejcik, J., Casneuf, T., Nijhof, I. S., Verbist, B. M. P., Bald, J., Plesner, T., Syed, K. W., Liu, K., van de Donk, N. W. C. J., Weiss, B. M., et al. (2016) · Blood · doi:10.1182/blood-2015-12-687749 · Cited by 961 · see citing works
LAG3 (CD223) as a Cancer Immunotherapy Target
Andrews, L. P., Marciscano, A., Drake, C., & Vignali, D. A. A. (2017) · Immunological Reviews · doi:10.1111/imr.12519 · Cited by 881 · see citing works
“As a result, the number of possible immunotherapy regimens has grown exponentially, giving rise to the rationale that synergistic combinations should yield significant clinical improvement compared with current monotherapies (13).”
BackgroundSelf-citationCombination cancer immunotherapies tailored to the tumour microenvironment
Smyth, M. J., Ngiow, S. F., Ribas, A., & Teng, M. W. L. (2016) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2015.209 · Cited by 944 · see citing works
Khoja, L., Day, D., Chen, T. W., Siu, L. L., & Hansen, A. R. (2017) · Annals of Oncology · doi:10.1093/annonc/mdx286 · Cited by 937 · see citing works
“agent [9, 11–35], 35% an anti-PD-1 agent [3, 4, 6–8, 36–47] and 4% an anti-PD-L1 ICI [48, 49].”
Microsatellite Instability as a Biomarker for PD-1 Blockade
Dudley, J. C., Lin, M., Le, D. T., & Eshleman, J. R. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-1678 · Cited by 934 · see citing works
- Authors
- 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., Pitot, H. C., Hamid, O., Bhatia, S., Martins, R., Eaton, K., Chen, S., Salay, T. M., Alaparthy, S., Grosso, J. F., Korman, A. J., Parker, S. M., Agrawal, S., Goldberg, S. M., Pardoll, D. M., Gupta, A., & Wigginton, J. M.
- Affiliations
- Johns Hopkins University (US)
- Seattle Cancer Care Alliance (US)
- The University of Texas MD Anderson Cancer Center (US)
- Baylor St. Luke's Medical Center (US)
- Winship Cancer Institute (US)
- Roswell Park Comprehensive Cancer Center (US)
- Mayo Clinic (US)
- Bristol-Myers Squibb (United States) (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2012-06-28
- Volume
- 366
- Issue
- 26
- Pages
- 2455-2465
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC3563263
- OpenAlex
- W2101653483
- Cited by
- 7,945
- References
- 39
- Citations by year
- 2026: 178 · 2025: 315 · 2024: 418 · 2023: 533 · 2022: 566 · 2021: 611 · 2020: 694 · 2019: 629 · 2018: 592 · 2017: 733 · 2016: 723 · 2015: 762 · 2014: 573 · 2013: 493 · 2012: 108
- FWCI
- 306.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR000454)
- National Cancer Institute (U10CA180802, P30CA015704, R01CA142779, P30CA006973)
- National Center for Research Resources (UL1RR024148)
- National Center for Advancing Translational Sciences
- 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
- PD-L1 inhibitors, PD-L1 blockade, PD-1/PD-L1 axis, immune checkpoint inhibitors, advanced cancer, non-small cell lung cancer, melanoma, renal cell carcinoma, ovarian cancer, treatment safety, objective response rate, antitumor immunity
- MeSH terms
- Nivolumab, Adult, Antibodies, Monoclonal, Antineoplastic Agents, Breast Neoplasms, Carcinoma, Non-Small-Cell Lung, Carcinoma, Renal Cell, Dose-Response Relationship, Drug, Female, Humans, Male, Melanoma, Neoplasms, Ovarian Neoplasms, Pancreatic Neoplasms, Stomach Neoplasms, Colorectal Neoplasms, 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
