TY - CHAP M1 - Book, Section TI - Immune Checkpoint Inhibitors A1 - Quezada, Sergio A. A1 - Peggs, Karl S. A2 - Kaushansky, Kenneth A2 - Prchal, Josef T. A2 - Burns, Linda J. A2 - Lichtman, Marshall A. A2 - Levi, Marcel A2 - Linch, David C. PY - 2021 T2 - Williams Hematology, 10e AB - SUMMARYT-cell function is tightly regulated in order to prevent inappropriate activation or collateral damage during productive immune responses. One of the critical cell intrinsic regulatory elements is a series of inhibitory cell surface receptors. In normal immune responses, the integration of signaling from the T-cell receptor (signal 1), costimulatory and coinhibitory receptors (signal 2), and further signals provided by cytokines (signal 3) determine cell fate and activation status. Lack of appropriate stimulatory elements or an abundance of inhibitory signals can drive anergy or exhaustion, preventing the immune system from responding to foreign antigens, particularly those presented chronically such as cancer neoantigens. Multiple elements of this rheostatic system are therefore potentially targetable to enhance immunity for therapeutic benefit. Drugs targeting the inhibitory signaling pathway checkpoints (checkpoint inhibitors) have shown efficacy in several human cancers, including hematologic malignancies, forming the basis for the award of the Nobel Prize for Medicine in 2018 to James P. Allison and Tasuku Honjo “for their discovery of cancer therapy by inhibition of negative immune regulation.” Insights into the pathways most relevant for immune evasion in specific cancers have underpinned significant clinical progress and offer promising areas for future research, often in combination with other therapeutic modalities. SN - PB - McGraw-Hill Education CY - New York, NY Y2 - 2024/04/17 UR - accessmedicine.mhmedical.com/content.aspx?aid=1178737701 ER -