Deadly distraction

A study led by Taha Merghoub, Jedd Wolchok and Andrew Chow, Ludwig investigators at Memorial Sloan Kettering (MSK), and Charles Rudin of MSK showed that immune cells known as macrophages residing in body cavities can aid tumor growth by distracting the immune system’s cancer-killing CD8+ T cells. The researchers reported in the June issue of Cancer Cell that cavity-resident macrophages express high levels of Tim-4, a receptor for phosphatidylserine (PS), a molecule they found to be highly expressed on activated and proliferative CD8+ T cells. Clinical samples revealed that while Tim-4 on such macrophages varied among lung cancer patients, those with higher levels of the receptor tended to have fewer CD8+ T cells responding to the tumor. The researchers explored whether blocking Tim-4 would enhance PD-1 blockade in mouse models of colon and lung cancer. While blocking Tim-4 alone didn’t reduce tumor growth or improve survival, it did enhance efficacy of PD-1 blockade and boost the numbers of CD8+ T cells in the peritoneal cavity. The researchers also showed in a preclinical model that Tim-4 blockade reduces immunosuppression in adoptive T-cell therapy, in which tumor targeting T cells are grown and re-infused into patients. The authors are exploring means to develop this approach for therapy.

This article appeared in the August 2021 issue of Ludwig Link. Click here to download a PDF (2MB).


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