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ReachMDStudy Finds Hallmarks of T Cell Exhaustion Within Hours of Tumor Exposure

The study used a genetic mouse model to track immune responses and study how T cells respond to tumors.

A recent study published in Nature Immunology reveals an unexpected finding about the rapid exhaustion of T cells upon encountering a tumor. Within a mere six to 12 hours, T cells that should be capable of attacking cancer cells become dysfunctional. This discovery challenges existing theories about T cell exhaustion and could have significant implications for cancer immunotherapies.

Key Points:

  • T cells become dysfunctional or “exhausted” within hours of encountering a tumor, a much faster time window than previously thought.
  • The findings include dramatic changes in chromatin accessibility and gene expression within six to 12 hours.
  • The changes in T cells were observed across different tumor types, and once dysfunctional, the T cells could not regain function.
  • Negative tumor signals can override functional programs in fully activated and functional T cells.

Additional Points:

  • The researchers also found certain trends, such as increased expression of inflammation-associated genes during infection, which are not turned on in the tumor model.
  • The team is exploring ways to boost T cell function through infection and other means of activating innate immune pathways.
  • The study builds on previous research that found thousands of differences in genes in tumor-activated T cells compared to infection-activated T cells.


  • The study’s findings challenge existing ideas about T cell exhaustion and may lead to more personalized and effective immunotherapies for cancer patients.

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“In patients who are diagnosed with cancer, we can’t go back in time to find out how the immune system responded. The mouse model allows us to do this, to say, ‘What is happening when T cells first see tumors; when and how do the T cells get exhausted?'”

Mary Philip, MD, PhD
Assistant Professor of Medicine, Division of Hematology and Oncology
Vanderbilt University Medical Center
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