{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Chow RD"],"funding":["Stand Up To Cancer","NCATS NIH HHS","Howard Hughes Medical Institute","National Cancer Institute","NCI NIH HHS","Discovery To Cure","National Institutes of Health","Paul and Daisy Soros Fellowships for New Americans","Fondazione Guido Berlucchi","Gilead Sciences","NIGMS NIH HHS","Merck"],"pagination":["312-331"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9905265"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13(2)"],"pubmed_abstract":["Mismatch repair-deficient (MMRd) cancers have varied responses to immune-checkpoint blockade (ICB). We conducted a phase II 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 with epigenetic MMRd; however, within each category of MMRd, mutation burden was not correlated with ICB response. Pretreatment JAK1 mutations were not associated with primary resistance to pembrolizumab. Longitudinal single-cell RNA-seq of circulating immune cells revealed contrasting modes of antitumor immunity for mutational versus epigenetic M"],"journal":["Cancer discovery"],"pubmed_title":["Distinct Mechanisms of Mismatch-Repair Deficiency Delineate Two Modes of Response to Anti-PD-1 Immunotherapy in Endometrial Carcinoma."],"pmcid":["PMC9905265"],"funding_grant_id":["P30CA16359","F30 CA239444","U01 CA176067","F30CA239444","U01CA176067-01A1","T32GM136651","Convergence Grant 2.0","F30 CA250249","T32 GM136651","UL1 TR001863","P30 CA016359","F30CA250249"],"pubmed_authors":["Bellone S","Hartwich TMP","Santin AD","Iwasaki A","Chow RD","Song E","Michaels T","Bonazzoli E"],"additional_accession":[]},"is_claimable":false,"name":"Distinct Mechanisms of Mismatch-Repair Deficiency Delineate Two Modes of Response to Anti-PD-1 Immunotherapy in Endometrial Carcinoma.","description":"Mismatch repair-deficient (MMRd) cancers have varied responses to immune-checkpoint blockade (ICB). We conducted a phase II 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 with epigenetic MMRd; however, within each category of MMRd, mutation burden was not correlated with ICB response. Pretreatment JAK1 mutations were not associated with primary resistance to pembrolizumab. Longitudinal single-cell RNA-seq of circulating immune cells revealed contrasting modes of antitumor immunity for mutational versus epigenetic M","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Feb","modification":"2026-05-29T07:45:16.832Z","creation":"2025-02-19T01:18:02.752Z"},"accession":"S-EPMC9905265","cross_references":{"pubmed":["36301137"],"doi":["10.1158/2159-8290.CD-22-0686","10.1158/2159-8290.cd-22-0686"]}}