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Remodeling of the Immune and Stromal Cell Compartment by PD-1 Blockade in Mismatch Repair-Deficient Colorectal Cancer

GSE205506 Homo sapiens Expression profiling by high throughput sequencing 40 samples Submitted 2023/05/11 Platform GPL29480Platform GPL24676
Summary
Immune checkpoint inhibitor (ICI) therapy can induce complete responses in mismatch repair-deficient and microsatellite instability-high (d-MMR/MSI-H) colorectal cancers (CRCs). However, the mechanism responsible for pathological complete response (pCR) to immunotherapy has not been completely understood. We utilize single-cell RNA sequencing to examine the immune and stromal cell dynamics in 19 patients with d-MMR/MSI-H CRC treated with the neoadjuvant PD-1 blockade. In tumors with a pCR, the proportions of CD8+ Trm-mitotic, CD4+ Tregs, proinflammatory IL1B monocyte and CCL2+Fibroblast concertedly decrease following treatment, while those of CD8+ Tem, CD4+ Th, CD20+ B and HLA-DRA+ Endothelial cells increase. Proinflammatory features in tumor microenvironment mediate the persistence of residual tumors by modulating CD8+ T cells and other response-associated immune cell populations. Our study provides rich resources and biological insights into the mechanism of successful ICI therapy and potential targets to improve treatment efficacy.
Published in
Remodeling of the immune and stromal cell compartment by PD-1 blockade in mismatch repair-deficient colorectal cancer
Li J, Wu C, Hu H et al. · Cancer cell 2023 · PMID 37172580 · doi:10.1016/j.ccell.2023.04.011
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Also filed as BioProject PRJNA846169. Searching any of these in the dataset finder brings you back here.

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