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How a protein implicated in Alzheimer's could enhance cancer immunotherapy

Variants of TREM2, a receptor expressed by immune cells, have been linked to the development of Alzheimer’s disease. Now scientists have shed light on a potential new use for the protein in cancer treatment.

TREM2 is also found in tumor-infiltrating myeloid cells, which sometimes create an immunosuppressive environment that helps tumors escape immune surveillance. In a study published in Cell, a team at Washington University School of Medicine in St. Louis showed that targeting the protein could be a potential new way to enhance the power of immuno-oncology drugs.

In tumor-bearing mice, treatment with an anti-TREM2 monoclonal antibody, combined with a PD-1 inhibitor, worked better at controlling tumor growth than either drug did alone, the team found.

To understand the role of TREM2 in anti-tumor immune responses, the researchers removed the gene that encodes the protein in mice and injected them with cancer cells. Compared with wild-type mice, these TREM2-lacking animals showed consistently reduced tumor progression.

Moreover, significantly more CD8+ and CD4+ T cells—which are critical to mounting an immune response against cancer—appeared to have been activated in TREM2-negative mice. This led the researchers to hypothesize that inhibiting TREM2 could improve responsiveness to anti-PD-1 blockade, which works by removing the “brakes” that tumors use to subdue immune cells.

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