Next-Generation Sequencing to Support Immuno-Oncology Therapy: The Emerging Role of Tumor Mutation Burden

Published: Friday, Aug 03, 2018
cancer
The introduction of immunotherapy has changed the treatment paradigm in cancer. Agents directed at immune checkpoint blockade obviate processes that inhibit antitumor activity of the native immune system, thereby restoring capacity to the cancer-immunity cycle.1 As cancer cells proliferate and accumulate genetic alterations, they express varying degrees of neoantigens, differentiation antigens, or cancer/testis antigens that become bound to major histocompatibility class I (MHCI) molecules on the surfaces of cancer cells. Under normal physiologic conditions, neoantigens produced by oncogenesis are captured by dendritic cells and are then presented to T cells via MHC class I and and class II (MHCII) molecules. In the presence of immunogenic signals, naïve T cells generate an anticancer response as opposed to a tolerant response to the antigen (ie, priming and activation of effector T cells). Activated effector T cells then migrate to the tumor site, infiltrate the tumor bed, interact with the antigen bound to the MHCI molecule, and ultimately recognize the original antigen as foreign, thus initiating immune activity that results in cell death.1
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Community Practice Connections™: New Directions in Advanced Cutaneous Squamous Cell Carcinoma: Emerging Evidence of ImmunotherapyAug 13, 20191.5
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