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Mutational and Antigenic Landscape in Tumor Progression and Cancer Immunotherapy

Ilio Vitale1, Antonella Sistigu2, Gwenola Manic3

  • 1Department of Biology, University of Rome 'Tor Vergata', Rome, Italy; IRCSS - Regina Elena National Cancer Institute, Rome, Italy; These authors contributed equally to this article; Co-senior authors.

Trends in Cell Biology
|February 16, 2019
PubMed

Insights

Cancer evolves with mutations that create tumor neoantigens (TNAs). Despite immune control, defects allow TNA accumulation, improving immunotherapy response. Strategies aim for immune control despite impaired immunosurveillance.

Area of Science:

  • Oncology
  • Immunology
  • Cancer Genomics

Background:

  • Neoplasms accumulate mutations, generating tumor neoantigens (TNAs) recognized by the immune system.
  • TNAs, arising outside central tolerance, are typically under immune control.
  • Impaired immune eradication and local immunosuppression can lead to TNA accumulation, correlating with immunotherapy sensitivity.

Purpose of the Study:

  • To investigate how tumor-intrinsic factors and immunological processes influence the mutational and antigenic landscape of evolving neoplasms.
  • To understand the impact of these landscapes on clinical responses to immunotherapy.
  • To propose strategies for achieving robust immunological control in the context of compromised immunosurveillance.

Main Methods:

  • Analysis of tumor mutational data and immune cell infiltration.
  • Correlation of neoantigen load with clinical outcomes in immunotherapy cohorts.
  • Exploration of genetic and microenvironmental factors affecting TNA expression and immune recognition.

Main Results:

  • Tumor evolution generates neoantigens that can be recognized by T cells.
  • Defects in immune surveillance and immunosuppressive tumor microenvironments facilitate TNA accumulation.
  • Higher TNA burden is associated with enhanced sensitivity to various immunotherapies.

Conclusions:

  • Tumor-intrinsic and immunological factors critically shape the antigenic landscape, influencing immunotherapy efficacy.
  • Strategies targeting these factors are crucial for overcoming immune evasion and achieving durable disease control.
  • Understanding TNA dynamics is key to developing more effective cancer immunotherapies.
Keywords:
adoptive cell transferantigen presentationimmune checkpoint blockersmutational loadoncolytic virotherapytumor microenvironment

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