Immune Activation in Mismatch Repair Deficient Carcinogenesis: More Than Just Mutational Rate.
Immune Activation in Mismatch Repair Deficient Carcinogenesis: More Than Just Mutational Rate.
Clin Cancer Res. 2019 Aug 05;:
Authors: Willis JA, Reyes-Uribe L, Chang K, Lipkin SM, Vilar E
Abstract
MMR-deficient colorectal cancers (dMMR CRC) are characterized by the expression of highly-immunogenic neoantigen peptides, which stimulate lymphocytic infiltration as well as up-regulation of inflammatory cytokines. These features are key to understanding why immunotherapy (specifically PD-1 and/or CTLA-4 checkpoint blockade) has proved to be highly effective for the treatment of patients with advanced dMMR CRC. Importantly, pre-clinical studies also suggest that this correlation between potent tumor neoantigens and the immune microenvironment is present in early (pre-malignant) stages of dMMR colorectal tumorigenesis as well, even in the absence of a high somatic mutation burden. Here, we discuss recent efforts to characterize how neoantigens and the tumor immune microenvironment co-evolve throughout the dMMR adenoma-to-carcinoma pathway. We further highlight how this pre-clinical evidence forms the rational basis for developing novel immunotherapy-based CRC prevention strategies for patients with Lynch syndrome.
PMID: 31383734 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Willis JA, Reyes-Uribe L, Chang K, Lipkin SM, Vilar E Tags: Clin Cancer Res Source Type: research
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