Table S1 from Distinct Mechanisms of Mismatch-Repair Deficiency Delineate Two Modes of Response to Anti–PD-1 Immunotherapy in Endometrial Carcinoma

Name: Table S1 from Distinct Mechanisms of Mismatch-Repair Deficiency Delineate Two Modes of Response to Anti–PD-1 Immunotherapy in Endometrial Carcinoma
Published: 2023-04-04T00:21:01+00:00
License: https://creativecommons.org/licenses/by/4.0/
Keywords: cancer

https://doi.org/10.1158/2159-8290.22541715

dataset

posted on 2023-04-04, 00:21 authored by Ryan D. Chow, Tai Michaels, Stefania Bellone, Tobias M.P. Hartwich, Elena Bonazzoli, Akiko Iwasaki, Eric Song, Alessandro D. Santin

<p>Supplementary Table S1: Genomic and clinical characteristics of the study cohort.</p>

Funding

National Institutes of Health (NIH)

National Cancer Institute (NCI)

United States Department of Health and Human Services

Find out more...

Howard Hughes Medical Institute (HHMI)

Paul and Daisy Soros Fellowships for New Americans (P.D. Soros Fellowship for New Americans)

Stand Up To Cancer (SU2C)

Discovery To Cure

Fondazione Guido Berlucchi

Gilead Sciences (Gilead)

Merck (Merck & Co.)

History

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

ARTICLE 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 MMRd cancers. Whereas effector CD8+ T cells correlated with regression of mutational MMRd tumors, activated CD16+ NK cells were associated with ICB-responsive epigenetic MMRd tumors. These data highlight the interplay between tumor-intrinsic and tumor-extrinsic factors that influence ICB response. The molecular mechanism of MMRd is associated with response to anti–PD-1 immunotherapy in endometrial carcinoma. Tumors with epigenetic MMRd or mutational MMRd are correlated with NK cell or CD8+ T cell–driven immunity, respectively. Classifying tumors by the mechanism of MMRd may inform clinical decision-making regarding cancer immunotherapy.This article is highlighted in the In This Issue feature, p. 247