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: Tags: Clin Cancer Res Source Type: research