Disarming the body’s defenders: Study shows how certain cancers neutralize T cells to subvert the immune system and help tumors grow

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.

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.

“Our study highlights an immune component in this type of cancer that wasn’t fully appreciated before,” said senior author Marcia Haigis, professor of cell biology in the Blavatnik Institute at HMS. “We now know that a metabolite produced by tumor cells can impact nearby immune cells to make the surrounding environment less hostile for the cancer.”

Fueling Cancer

For the past 15 years, the Haigis lab has been studying the mechanisms that fuel cancer, including tumor metabolites that help cancer cells survive and grow. The research led Haigis and colleagues to the immune system, which works to suppress tumor growth by dispatching immune cells into the tumor microenvironment to kill tumor cells. But how exactly do tumor and immune cells interact? Why do certain tumors survive the immune attack, while others do not?

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