-cell immune response ( Figure 2 ). These additional signals for optimal T-cell priming involve agonist coreceptors, such as CD28, 4-1BB, and OX40, and inhibitory coreceptors, such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-1 (PD-1
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Saby George, Roberto Pili, Michael A. Carducci, and Jenny J. Kim
Nancy Danielle Ebelt, Edith Zuniga, and Edwin Ramos Manuel
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. Immune checkpoint blockers (ICBs) composed of antibodies targeting programmed death 1 (anti-PD1) and cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4
John A. Thompson
grades 3–5 immunotherapy-related AEs occur with greater frequency with CTLA-4 inhibitors than with PD-1 or PD-L1 inhibitors. Toxicity is also more severe with combinations of CTLA-4 with PD-1 or PD-L1 inhibitors than with either class of agent alone
John A. Thompson, Bryan J. Schneider, Julie Brahmer, Stephanie Andrews, Philippe Armand, Shailender Bhatia, Lihua E. Budde, Luciano Costa, Marianne Davies, David Dunnington, Marc S. Ernstoff, Matthew Frigault, Brianna Hoffner, Christopher J. Hoimes, Mario Lacouture, Frederick Locke, Matthew Lunning, Nisha A. Mohindra, Jarushka Naidoo, Anthony J. Olszanski, Olalekan Oluwole, Sandip P. Patel, Sunil Reddy, Mabel Ryder, Bianca Santomasso, Scott Shofer, Jeffrey A. Sosman, Momen Wahidi, Yinghong Wang, Alyse Johnson-Chilla, and Jillian L. Scavone
of ICI immunotherapy differ greatly from that of cytotoxic chemotherapy or targeted anticancer therapy. 3 Similarly, anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and anti-PD-1/PD-L1 immunotherapies are associated with toxicity profiles
Margaret Tempero
understood. And until now, the primary importance of knowing who carried pathologic germline mutations was for screening and early detection, not disease management. The success of checkpoint inhibitors (antibodies to CTLA-4, PD-1, or PD-L1) has been
Leslie A. Fecher and Keith T. Flaherty
cells and clinical outcome in patients with high-risk melanoma treated with adjuvant granulocyte macrophage colony-stimulating factor . J Clin Oncol 2008 ; 26 : 3235 – 3241 . 33 O’Day S Hamid O Urba W . Targeting CTLA-4: a novel strategy
Anthony J. Olszanski
to the treatment paradigm has dramatically impacted survival in patients with melanoma. CTLA-4 and PD-1/PD-L1 immune checkpoints are negative regulators of T-cell immune function. PD-L1 binds to PD-1 and inhibits T-cell killing of the tumor cell, but
NCCN Guidelines Insights: Management of Immunotherapy-Related Toxicities, Version 1.2020
Featured Updates to the NCCN Guidelines
John A. Thompson, Bryan J. Schneider, Julie Brahmer, Stephanie Andrews, Philippe Armand, Shailender Bhatia, Lihua E. Budde, Luciano Costa, Marianne Davies, David Dunnington, Marc S. Ernstoff, Matthew Frigault, Benjamin H. Kaffenberger, Matthew Lunning, Suzanne McGettigan, Jordan McPherson, Nisha A. Mohindra, Jarushka Naidoo, Anthony J. Olszanski, Olalekan Oluwole, Sandip P. Patel, Nathan Pennell, Sunil Reddy, Mabel Ryder, Bianca Santomasso, Scott Shofer, Jeffrey A. Sosman, Yinghong Wang, Ryan M. Weight, Alyse Johnson-Chilla, Griselda Zuccarino-Catania, and Anita Engh
checkpoints are part of the natural balance of the immune system to prevent autoimmunity and are exploited by cancer cells to suppress the immune response. Immune checkpoint inhibitors (ICIs) block proteins—namely PD-1, PD-L1, and CTLA-4—that allow tumor cells
Cesar A. Santa-Maria and Rita Nanda
immune system, including CTLA-4, PD-1, and PD-L1. CTLA-4 inhibitors were the first immune checkpoint inhibitors (ICIs) to demonstrate a benefit in melanoma; subsequently PD-1/PD-L1 inhibitors have shown response rates across a wide variety of cancers
Van K. Morris and Cathy Eng
checkpoint regulators such as PD-1 and CTLA-4 bind their respective receptors on T cells to abrogate T-cell activity. 17 , 18 Because of their ability to present mutated proteins identifiable as “non-self” epitopes to circulating immune cells, tumor cells
