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'Final common pathway' of human cancer immunotherapy: targeting random somatic mutations

Eric Tran1, Paul F Robbins1, Steven A Rosenberg1

  • 1Surgery Branch, National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland, USA.

Nature Immunology
|February 16, 2017
PubMed

Insights

Cancer immunotherapies like adoptive cell transfer (ACT) are effective, but targets remain unclear. Research suggests T cells targeting tumor neoantigens from cancer mutations are key mediators of successful human cancer immunotherapies.

Area of Science:

  • Immunology
  • Oncology
  • Genetics

Background:

  • Effective cancer immunotherapies, including cytokine IL-2, adoptive cell transfer (ACT), and checkpoint blockade (CTLA-4, PD-1), have advanced without fully identifying their in vivo targets.
  • Adoptive cell transfer (ACT) with autologous lymphocytes offers a direct method to study the antigen recognition driving human cancer regression.

Purpose of the Study:

  • To investigate the immunogenic targets of effective human cancer immunotherapies.
  • To explore the role of tumor neoantigens in mediating anti-tumor immune responses.

Main Methods:

  • Utilizing high-throughput immunological testing of lymphocytes from cancer patients undergoing ACT.
  • Employing deep sequencing of autologous tumors to identify cancer mutations and neoantigens.

Main Results:

  • Identified T cells targeting tumor neoantigens as the primary mediators of many successful human cancer immunotherapies.
  • Characterized the incidence and molecular basis of anti-tumor lymphocytes in cancer patients.

Conclusions:

  • T cells recognizing neoantigens derived from cancer mutations are crucial for effective cancer immunotherapy.
  • Understanding these neoantigen targets can refine and improve future cancer immunotherapy strategies.

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