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Saul J. Priceman, Yukiko Yamaguchi, Elizabeth Epps, John Burnett, and Stephen J. Forman

. Immune checkpoint pathways, including the programmed cell death protein-1 (PD-1) and the cytotoxic T lymphocyte-associated protein-4 (CTLA4), have emerged as critical drivers of immunosuppression in solid cancers, by limiting both adaptive antitumor

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Antoni Ribas

; 18 : 3964 – 3973 . 58. Chen L Ashe S Brady WA . Costimulation of antitumor immunity by the B7 counterreceptor for the T lymphocyte molecules CD28 and CTLA-4 . Cell 1992 ; 71 : 1093 – 1102 . 59. Bluestone JA . Is CTLA-4 a

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Kavea Panneerselvam, Rajan N. Amin, Dongguang Wei, Dongfeng Tan, Phillip J. Lum, Hao Chi Zhang, David M. Richards, Mehmet Altan, Petros Grivas, John A. Thompson, Anusha S. Thomas, and Yinghong Wang

Background Immune checkpoint inhibitors (ICIs) are revolutionary agents that are increasingly used to treat a variety of malignancies. 1 – 3 These agents typically target inhibitory regulators of T cells, including CTLA-4, PD-1, and PD-L1

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Neil J. Shah, Michael R. Cook, Tianmin Wu, Shaked Lev-Ari, Matthew J. Blackburn, Michael T. Serzan, Adil Alaoui, Jaeil Ahn, and Michael B. Atkins

Background Immune checkpoint inhibitor (ICI) therapies have revolutionized the treatment of many advanced cancers. ICIs are monoclonal antibodies that block key immune checkpoints, including PD-1, PD-L1, and CTLA-4, 1 , 2 leading to the

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Andrew J. Portuguese, Scott S. Tykodi, Christopher D. Blosser, Ted A. Gooley, John A. Thompson, and Evan T. Hall

coinhibitory signaling on activated T cells. Since FDA approval of the first immune checkpoint inhibitor (ICI), ipilimumab, in 2011, 8 ICIs have been approved that target CTLA-4 (ie, ipilimumab), PD-1 (ie, nivolumab, pembrolizumab, cemiplimab, dostarlimab), or

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Wells A. Messersmith

In the last year, several impactful updates have been added to the NCCN Guidelines for Colorectal Cancer (CRC) for the management of metastatic disease, including additional options for BRAF-mutated advanced CRC and the inclusion of combination immunotherapy (PD-1 and CTLA-4) for deficient mismatch repair/microsatellite instability (MSI)–high advanced CRC. According to Dr. Wells A. Messersmith, targeted therapies (ie, VEGFR, EGFR, multitargeted tyrosine kinase inhibitors) play an important role in CRC management, but none of them have been successful in the adjuvant setting (although checkpoint inhibition is now being tested in MSI-high stage III CRC). Reliable predictive biomarkers for most agents are still greatly lacking, highlighting the importance of investing in CRC biomarker studies.

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Alan N. Houghton

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Rodger J. Winn

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Laura C. Kennedy, Shailender Bhatia, John A. Thompson, and Petros Grivas

–associated antigen (CTLA-4) agents (ipilimumab, tremelimumab). The PD-1/PD-L1 and CTLA-4 pathways provide negative feedback to naturally downregulate appropriate immune responses and also guard against inappropriate or autoimmune responses. In a tumor, these pathways

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Anthony J. Olszanski

cancer,” he added. In the 21st century, the first cancer vaccine was approved worldwide in Russia for renal cell carcinoma in 2008. In fairly rapid succession, sipuleucel-T was approved for prostate cancer, the CTLA-4 inhibitor ipilimumab was approved