Transcriptomics

Dataset Information

0

Distinct Mechanisms of Mismatch-Repair Deficiency Delineate Two Modes of Response to Anti–PD-1 Immunotherapy in Endometrial Carcinoma


ABSTRACT: Responses to immune checkpoint blockade (ICB) are variable among mismatch repair-deficient (MMRd) cancers. We completed a phase 2 clinical trial of the PD-1 inhibitor pembrolizumab in 24 patients with MMRd endometrial cancer (NCT02899793). Patients with mutational MMRd tumors (6 patients) had higher response rates and longer survival than those with epigenetic MMRd tumors (18 patients). Mutation burden was higher in tumors with mutational MMRd compared to epigenetic MMRd; however, within each category of MMRd, mutation burden was not associated with ICB response. Notably, JAK1 mutations did not confer resistance to pembrolizumab. Longitudinal single-cell RNA-seq of circulating immune cells revealed contrasting modes of anti-tumor immunity against mutational and epigenetic MMRd cancers. Whereas effector CD8+ T cell responses correlated with regression of mutational MMRd tumors, highly active CD16+ NK cells were associated with ICB-responsive epigenetic MMRd tumors. These data highlight the interplay between tumor-intrinsic and extrinsic factors that influence ICB response.

ORGANISM(S): Homo sapiens

PROVIDER: GSE212217 | GEO | 2022/10/07

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2024-07-19 | GSE268903 | GEO
2024-07-23 | MODEL2407210002 | BioModels
2024-07-23 | MODEL2407210001 | BioModels
| 2272487 | ecrin-mdr-crc
2023-10-31 | GSE246684 | GEO
2024-01-01 | E-MTAB-12922 | biostudies-arrayexpress
2022-08-17 | GSE208614 | GEO
2021-08-26 | GSE178341 | GEO
2019-08-13 | GSE132035 | GEO
2019-08-13 | GSE131927 | GEO