The following is a summary of “Remodeling of the immune and stromal cell compartment by PD-1 blockade in mismatch repair-deficient colorectal cancer,” published in the July 2023 issue of the Cancer Cell by Li et al.
Immune checkpoint inhibitor (ICI) therapy can induce complete responses in colorectal cancers (CRCs) with deficient mismatch repair and elevated microsatellite instability (d-MMR/MSI-H). However, the underlying mechanism for immunotherapy-induced pathological complete response (pCR) must still be fully understood.
The researchers investigated the dynamics of immune and stromal cells in 19 patients with d-MMR/MSI-H CRC who received neoadjuvant PD-1 blockade using single-cell RNA sequencing (scRNA-seq). The proportions of CD8+ Tem, CD4+ Th, CD20+ B, and HLA-DRA+ Endothelial cells increase in tumors with pCR, whereas the proportions of CD8+ Trm-mitotic, CD4+ Tregs, proinflammatory IL1B+ Mono, and CCL2+ Fibroblast decrease.
By modulating CD8+ T cells and other response-associated immune cell populations, proinflammatory aspects of the tumor microenvironment contribute to the persistence of residual tumors. Their research provides valuable biological insights into the mechanism of effective ICI therapy and potential targets for enhancing treatment efficacy.