A Functionally Constrained Immune Ecosystem in Microsatellite-stable Colorectal Cancer Resolved by Single-cell and Exome Profiling.
Wenxu Liu, Yipan Zheng, Hao Wang et al.
✦ AI-curated · Sources linked
Case in brief
A 77-year-old woman underwent resection of a mismatch repair-proficient, microsatellite-stable colorectal cancer with low mutational burden and a synchronous adenoma. Whole-exome sequencing found no shared high-confidence somatic mutations between the cancer and adenoma within the assay’s sensitivity, while identifying tumor-specific APC, KRAS and TP53 alterations. Single-cell RNA sequencing of the tumor found that T-lineage cells made up 83.5% of 7,569 cells. These included cytotoxic T cells with cytolytic and dysfunction-associated features, suppressively remodeled regulatory T cells, and Th17 cells with inflammatory and profibrotic programs.
What made this case unusual
Despite abundant T-lineage infiltration, the tumor’s immune profile included dysfunction-associated cytotoxic T cells and suppressive regulatory T-cell remodeling, suggesting that T-cell abundance did not equate to effective antitumor immunity.
Diagnostic / clinical pearl
In MSS colorectal cancer, a T-cell-rich tumor may still show features of constrained immune function; immune-cell abundance alone does not establish effective antitumor activity.