Association of Polymerase e-Mutated and Microsatellite-Instable Endometrial Cancers With Neoantigen Load, Number of Tumor-Infiltrating Lymphocytes, and Expression of PD-1 and PD-L1.

JAMA Oncol
Authors
Keywords
Abstract

IMPORTANCE: Immune checkpoint inhibitor therapy has shown benefit in various cancers, but their potential in endometrial cancer (EC) is unknown.

OBSERVATIONS: Prediction of neoantigen load was performed using sequencing data from the Cancer Genome Atlas data set. Evaluation of tumor-infiltrating lymphocytes (TILs) and PD-1 and PD-L1 expression was performed in 63 patients with EC referred to our institution. The predicted median (range) neoantigen load (predicted neoepitopes per sample) was proportional to the mutational load: highest in ultramutated polymerase e (POLE) tumors (8342 [628-20 440]), less in hypermutated MSI (541 [146-8063]; P

CONCLUSIONS AND RELEVANCE: Polymerase e-mutated and MSI ECs are associated with high neoantigen loads and number of TILs, which is counterbalanced by overexpression of PD-1 and PD-L1. Polymerase e-mutated and MSI EC tumors may be excellent candidates for PD-1-targeted immunotherapies.

Year of Publication
2015
Journal
JAMA Oncol
Volume
1
Issue
9
Pages
1319-23
Date Published
2015 Dec
ISSN
2374-2445
DOI
10.1001/jamaoncol.2015.2151
PubMed ID
26181000
Links
Grant list
1R01CA155010-04 / CA / NCI NIH HHS / United States