Mutational and Antigenic Landscape in Tumor Progression and Cancer Immunotherapy

Ilio Vitale, Antonella Sistigu, Gwenola Manic, Nils Petter Rudqvist, Zlatko Trajanoski, Lorenzo Galluzzi

Research output: Contribution to journalReview articlepeer-review

Abstract

Evolving neoplasms accumulate non-synonymous mutations at a high rate, potentially enabling the expression of antigenic epitopes that can be recognized by the immune system. Since they are not covered by central tolerance, such tumor neoantigens (TNAs) should be under robust immune control as they surge. However, genetic defects that impair cancer cell eradication by the immune system coupled with the establishment of local immunosuppression can enable TNA accumulation, which is generally associated with improved clinical sensitivity to various immunotherapies. Here, we explore how tumor-intrinsic factors and immunological processes shape the mutational and antigenic landscape of evolving neoplasms to influence clinical responses to immunotherapy, and propose strategies to achieve robust immunological control of the disease despite disabled immunosurveillance.

Original languageEnglish
Pages (from-to)396-416
Number of pages21
JournalTrends in Cell Biology
Volume29
Issue number5
DOIs
Publication statusPublished - May 2019

Keywords

  • adoptive cell transfer
  • antigen presentation
  • immune checkpoint blockers
  • mutational load
  • oncolytic virotherapy
  • tumor microenvironment

ASJC Scopus subject areas

  • Cell Biology

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