High-plex spatial transcriptomic profiling of mismatch repair-deficient endometrial cancer [GeoMx]

Tumors bearing mismatch repair deficiency (MMRd) are characterized by a high load of neoantigens and are believed to trigger immunogenic reactions upon immune checkpoint blockade treatment. However, multiple cancers with MMRd exhibit variable responses to immune checkpoint inhibitors (ICIs). In endometrial cancer (EC), a distinct tumor microenvironment (TME) exists that may correspond to treatment-related efficacies. Since pre-existing CD8+T cells in the TME are critical for effective treatment of ICI, and lack of T cell infiltration can make MMRd tumor insensitive to ICI therapy, we characterized MMRd ECs with different level of CD8+T cells infiltration. Our analysis identified a gene signature in the MMRd tumor-enriched regions stratifying tumors into “hot”, “intermediate” and “cold” groups according to their distinct immune profiles, a finding highly consistent with the corresponding CD8+ T-cell infiltration status. We applied digital spatial profiling, a high-plex spatial transcriptomic approach covering over 1,800 genes, to obtain a highly resolved TME landscape in 45 MMRd-EC patients. Please note that none of the patients (in the records) were treated with ICI. Since pre-existing CD8+T cells in the TME are critical for effective treatment of ICI, MMRd ECs with different level of CD8+T cells infiltration were analyzed. The CD8+T cells infiltration status is provided in each sample records.