Disarming the Body’s Defenders

Study shows how certain cancers neutralize T cells to subvert the immune system and help tumors grow

An illustration of a cluster of cancer cells forming a tumor
Principal investigator Marcia Haigis describes her new study on how cancer cells manipulate the immune system. Video: Shraddha Nayak, Grace Hsu, Janet Iwasa, and Rick Groleau

When cancer arises in the body, it starts with tumor cells that rapidly grow and divide and eventually spread. But what enables these nascent tumor cells to dodge the body’s immune system, which is built to identify and fend off an attack from such defective cells? The answer to this question, which long mystified scientists, may be the key to unlocking more effective cancer treatments — therapies that disable tumors’ subversive maneuvers and allow the immune system to do its job.

Now, a team led by researchers at Harvard Medical School has identified a way that tumor cells can turn off the immune system, allowing the tumor to grow unchecked. The research, conducted primarily in mice and published Sept. 29 in Science, shows that tumor cells with a particular mutation release a chemical, a metabolite, that weakens nearby immune cells, rendering them less capable of killing cancer cells.

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The findings reveal critical details of how tumors deactivate the immune system and highlight the role of tumor metabolites in this process. The results also point to the essential role that the area around the tumor — the tumor microenvironment — plays in cancer growth.

If elucidated through further research, the results could eventually help scientists develop better, more targeted therapies to treat cancers whose growth is fueled by this mechanism.