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TREM2 blockade modifies the tumor myeloid landscape enhancing anti-PD-1 immunotherapy

ABSTRACT: Checkpoint immunotherapy unleashes T cell effector functions that control tumor growth, but can be undermined by myeloid cells that induce immunosuppression. TREM2 is a myeloid surface receptor that binds lipids and transmits intracellular signals through protein-tyrosine phosphorylation known to sustain microglial responses during Alzheimer’s disease. Intriguingly, TREM2 expression has recently been noted in tumor-infiltrating macrophages. We found that Trem2–/– mice are more resistant to growth of sarcoma, colorectal and mammary cancer cells than wild-type mice and are more responsive to anti-PD-1 immunotherapy. Furthermore, treatment with anti-TREM2 mAb curbed tumor growth and led to complete tumor regression when combined with anti-PD-1. scRNA-seq revealed that both constitutive TREM2 deficiency and anti-TREM2 are associated with relatively scant representation of MRC1+ and CX3CR1+ subsets in the macrophage tumor infiltrate, paralleled by expansion of subsets expressing immunostimulatory molecules. These changes were associated with improved T cell responses. TREM2 expression was evident in tumor macrophages in over 200 human cancer cases examined and inversely correlated with prolonged survival for two types of cancer. Thus, TREM2 is a promising target to modify tumor-infiltrating myeloid cells and effectively augment checkpoint immunotherapy.

ORGANISM(S): Mus musculus

PROVIDER: GSE151710 | GEO | 2020/08/13

REPOSITORIES: GEO

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Lack of TREM2 during anti-PD-1 therapy reprograms intestinal macrophages and microbiota to enhance tumor rejection

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TREM2 blockade modifies the tumor myeloid landscape enhancing anti-PD-1 immunotherapy

Project description:TREM2 blockade modifies the tumor myeloid landscape enhancing anti-PD-1 immunotherapy

| PRJNA637036 | ENA

RNA-seq in KPC mice treated with a hypomethylating drug (decitabine) and in untreated KPC mice

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