To Boost Cancer Immunotherapy’s Fighting Power, Look to the Gut

Study reveals gut microbes alter body’s response to cancer immunotherapy

Closeup of a colon against a physicians' white coat and white gloves

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At a glance:

  • Immunotherapy has redefined cancer treatment, but not all patients experience the same benefit when treated.
  • New research in mice identifies how gut bacteria alter the body’s response to a common form of cancer immunotherapy.
  • The animals’ gut microbiota lowered the expression of two immune molecules, one previously unknown to play a role in cancer.
  • Using antibodies to block the activity of either molecule, or the interplay between them, enhanced response to cancer immunotherapy.
  • The findings can inform the design of treatments that boost the efficacy of cancer immunotherapy among patients with suboptimal response.

Cancer immunotherapy has transformed the treatment of many types of cancer. Yet, for reasons that remain poorly understood, not all patients get the same benefit from these powerful therapies.

One potent factor in treatment outcome appears to be an individual’s gut microbiota — the trillions of microorganisms that live in the human intestine — according to new research led by investigators at Harvard Medical School and Dana-Farber Cancer Institute.

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The study, done in mice and published May 3 in Nature, pinpoints how gut microbes enhance the body’s response to a common type of immunotherapy known as PD-1 checkpoint blockade, currently used for the treatment of 25 forms of cancer.

The research found that specific gut bacteria can affect the activity of two immune molecules — PD-L2 and RGMb — as well as the interplay between them.

The work also showed that blocking the activity of either molecule or the interplay between them enhanced responses to cancer immunotherapy and optimized the body’s ability to detect and destroy cancer cells.

“The engagement between PD-L2 and RGMb acts as a brake on cancer-fighting T cells, and our work shows that treatment with antibodies that block the interaction of PD-L2 with RGMb releases this brake and allows T cells to eradicate tumors,” said co-senior author Arlene Sharpe, the Kolokotrones University Professor at Harvard and chair of the Department of Immunology in the Blavatnik Institute at HMS.