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Immunology of Lynch Syndrome

Authors
  • Pastor, Danielle M.1, 1
  • Schlom, Jeffrey1
  • 1 National Institutes of Health, Bethesda, MD, USA , Bethesda (United States)
Type
Published Article
Journal
Current Oncology Reports
Publisher
Springer-Verlag
Publication Date
Jun 14, 2021
Volume
23
Issue
8
Identifiers
DOI: 10.1007/s11912-021-01085-z
Source
Springer Nature
Keywords
Disciplines
  • Topical Collection on Immuno-oncology
License
Green

Abstract

Purpose of ReviewPatients with Lynch syndrome have a high probability of developing colorectal and other carcinomas. This review provides a comprehensive assessment of the immunologic aspects of Lynch syndrome pathogenesis and provides an overview of potential immune interventions for patients with Lynch syndrome polyps and Lynch syndrome–associated carcinomas.Recent FindingsImmunogenic properties of the majority of Lynch syndrome polyps and associated cancers include microsatellite instability leading to a high mutational burden and the development of novel frameshift peptides, i.e., neoantigens. In addition, patients with Lynch syndrome develop T cell responses in the periphery and in the tumor microenvironment (TME) to tumor-associated antigens, and a proinflammatory cytokine TME has also been identified. However, Lynch syndrome lesions also possess immunosuppressive entities such as alterations in MHC class I antigen presentation, TGFβ receptor mutations, regulatory T cells, and upregulation of PD-L1 on tumor-associated lymphocytes.SummaryThe rich immune microenvironment of Lynch syndrome polyps and associated carcinomas provides an opportunity to employ the spectrum of immune-mediating agents now available to induce and enhance host immune responses and/or to also reduce immunosuppressive entities. These agents can be employed in the so-called prevention trials for the treatment of patients with Lynch syndrome polyps and for trials in patients with Lynch syndrome–associated cancers.

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