CASE REPORT article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1616361
This article is part of the Research TopicCommunity Series in Novel Biomarkers for Predicting Response to Cancer Immunotherapy: Volume IIIView all 18 articles
Lysine Methyltransferase 2D Deficiency Drives Complete Response to Pembrolizumab in PD-L1-High Cholangiocarcinoma :a case report and review of literature
Provisionally accepted
- Shanxi Bethune Hospital, Shanxi Medical University, Taiyuan, China
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Background: Intrahepatic cholangiocarcinoma (ICC) typically exhibits poor responsiveness to immune checkpoint inhibitors (ICIs) due to its microsatellite-stable (MSS) status and low tumor mutational burden (TMB). Conventional biomarkers like PD-L1 expression show limited predictive value, creating an urgent need for novel therapeutic targets in this aggressive malignancy.We describe a stage IV ICC patient with PD-L1 positivity and a somatic KMT2D mutation (p.R5303C) who attained sustained complete remission after pembrolizumab treatment, despite developing severe multi-organ immune-related adverse events (irAEs) including hepatitis, pneumonitis, and thrombocytopenia. Mechanistic analysis revealed that KMT2D deficiency potentially remodeled the tumor immune microenvironment through epigenetic reprogramming, characterized by enhanced CD8+ T-cell infiltration.Our findings advocate for combinatorial biomarker strategies incorporating epigenetic markers (KMT2D status) with PD-L1 expression to optimize ICI patient selection, while highlighting the need for vigilant toxicity monitoring in this subset.
Keywords: KMT2D Mutations, intrahepatic cholangiocarcinoma, immune checkpoint therapy, predictive biomarkers, Pathologic complete response
Received: 22 Apr 2025; Accepted: 28 Jul 2025.
Copyright: © 2025 Li, Wang 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: Liao Wang, Shanxi Bethune Hospital, Shanxi Medical University, Taiyuan, China
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