Related Experiment Video

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Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells
09:04

Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells

Published on: March 7, 2025

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The adaptive immune system is a major driver of selection for tumor suppressor gene inactivation

Timothy D Martin1, Rupesh S Patel1, Danielle R Cook2,3

  • 1Division of Genetics, Brigham and Women's Hospital, Howard Hughes Medical Institute, Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.

Science (New York, N.Y.)
|September 16, 2021
PubMed

Insights

Tumors evade the immune system by losing tumor suppressor genes (TSGs), especially when the adaptive immune system is present. This immune evasion drives cancer mutation patterns.

Area of Science:

  • Immunology
  • Oncology
  • Genetics

Background:

  • Tumors evolve to evade immune detection during tumorigenesis.
  • Mechanisms include disrupting antigen presentation and up-regulating inhibitory immune checkpoints.

Purpose of the Study:

  • To investigate genetic requirements for tumorigenesis under adaptive immune pressure.
  • To identify genes preferentially lost during tumor evolution in an immune-competent environment.

Main Methods:

  • In vivo CRISPR screens were employed in syngeneic mouse tumor models.
  • Comparisons were made between tumors with and without adaptive immune selective pressure.

Main Results:

  • A significant enrichment for the loss of tumor suppressor genes (TSGs) was observed in the presence of an adaptive immune system.
  • Nearly one-third of TSGs showed preferential enrichment, with cancer- and tissue-specific patterns.
  • This enrichment was more pronounced compared to immunocompromised mice.

Conclusions:

  • The adaptive immune system exerts selective pressure favoring the loss of specific TSGs during tumorigenesis.
  • Tumor evolution and the selection of recurrent mutations are significantly influenced by the need to evade immune surveillance.

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