Skip to main content

ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1528532
This article is part of the Research Topic Community Series in Novel Biomarkers for Predicting Response to Cancer Immunotherapy: Volume III View all 4 articles

Unveiling Immunogenic Characteristics and Neoantigens in Endometrial Cancer with POLE Hotspot Mutations for Improved Immunotherapy

Provisionally accepted
Xueli Zhang Xueli Zhang 1Jian Huang Jian Huang 2Shuangna Song Shuangna Song 2Yihua Yin Yihua Yin 2Yinyan He Yinyan He 2Huimin Wang Huimin Wang 2Ye Gu Ye Gu 2Laman He Laman He 2Xintao Wang Xintao Wang 2Xiaocao Miao Xiaocao Miao 1Zhigang Zhang Zhigang Zhang 1Yiran Li Yiran Li 2*
  • 1 Shanghai Cancer Institute, Shanghai, China
  • 2 Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Shanghai, Shanghai, China

The final, formatted version of the article will be published soon.

    Background Immunotherapy, especially with the use of immune checkpoint inhibitors, has demonstrated efficacy for a variety of malignant tumors. However, the potential of immunotherapy for endometrial cancer (EC) with POLE mutations remains underexplored. Methods We utilized multiple databases and clinical specimens to investigate the immunogenicity profiles of EC patients carrying POLE mutations. One particular hotspot mutation POLEP286R was identified and further studied. Consequently, by constructing human leukocyte antigen (HLA) tetramers and incubating them with patients' peripheral blood mononuclear cells (PBMCs), T cells capable of recognizing the POLEP286R mutation were sorted for further transcriptomic, proteomic and T-cell receptor (TCR) sequencing analyses and for an organoid EC model. Results Tumor- and immune-related pathways were shown to be activated in the POLEP286R mutant group. Importantly, by using an organoid model of EC, we further confirmed the antitumor potential of T cells that were specific to the POLEP286R mutation. Conclusions Our study uncovers the pronounced immunogenicity of POLE-mutant EC and characterizes neoantigens that are unique to the POLEP286R mutation, thus providing a promising new immunotherapeutic strategy for EC. Keywords Endometrial cancer (EC), POLE, tumor neoantigens, immunotherapy, CD8+ T cells

    Keywords: Endometrial cancer (EC), pole, tumor neoantigens, Immunotherapy, CD8 + T cells

    Received: 15 Nov 2024; Accepted: 06 Jan 2025.

    Copyright: © 2025 Zhang, Huang, Song, Yin, He, Wang, Gu, He, Wang, Miao, Zhang and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Yiran Li, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Shanghai, Shanghai, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.