Transcriptomics

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Crosstalk between CAR T cell subsets and the tumor microenvironment is essential for sustained cytotoxic activity


ABSTRACT: Chimeric antigen receptor (CAR) T cell therapy relies on the activity of a large pool of tumor-targeting cytotoxic effectors. Whether CAR T cells act autonomously or require interactions with the tumor microenvironment (TME) is unclear. Here, we report an essential crosstalk between CAR T cell subsets and the TME for tumor control. Using single-cell RNA sequencing, we revealed profound modification of the TME during CAR T cell therapy. IFN-gamma produced by CAR T cells and host-derived IL-12 not only enhanced endogenous T and NK cell activity but were also essential for sustaining CAR T cell cytotoxicity as revealed by intravital imaging. Compared to CD8+ CAR T cells, CD4+ CAR T cells were more efficient at host immune activation but less capable of tumor killing. In sum, CAR T cells are not acting alone in vivo but rely instead on a cytokine-mediated crosstalk with the TME for optimal activity. Invigorating CAR T cell interplay with the host represents an attractive strategy to prevent relapses.

ORGANISM(S): Mus musculus

PROVIDER: GSE165797 | GEO | 2021/03/29

REPOSITORIES: GEO

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