Mechanistic insights into lethal hyper progressive disease induced by PD-L1 inhibitor in metastatic urothelial carcinoma

IF 6.8 1区医学 Q1 ONCOLOGY

NPJ Precision Oncology Pub Date : 2024-09-17 DOI:10.1038/s41698-024-00707-6

Kazuki Nishimura, Kiyoshi Takahara, Kazumasa Komura, Mitsuaki Ishida, Kensuke Hirosuna, Ryoichi Maenosono, Masahiko Ajiro, Moritoshi Sakamoto, Kengo Iwatsuki, Yuki Nakajima, Takuya Tsujino, Kohei Taniguchi, Tomohito Tanaka, Teruo Inamoto, Yoshinobu Hirose, Fumihito Ono, Yoichi Kondo, Akihide Yoshimi, Haruhito Azuma

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Abstract

Hyper progressive disease (HPD) is a paradoxical phenomenon characterized by accelerated tumor growth following treatment with immune checkpoint inhibitors. However, the pathogenic causality and its predictor remain unknown. We herein report a fatal case of HPD in a 50-year-old man with metastatic bladder cancer. He had achieved a complete response (CR) through chemoradiation therapy followed by twelve cycles of chemotherapy, maintaining CR for 24 months. Three weeks after initiating maintenance use of a PD-L1 inhibitor, avelumab, a massive amount of metastases developed, leading to the patient’s demise. Omics analysis, utilizing metastatic tissues obtained from an immediate autopsy, implied the contribution of M2 macrophages, TGF-β signaling, and interleukin-8 to HPD pathogenesis.

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PD-L1抑制剂诱发转移性尿路上皮癌致命性超进展疾病的机理研究

超进展性疾病（HPD）是一种自相矛盾的现象，其特点是使用免疫检查点抑制剂治疗后肿瘤生长加速。然而，其致病原因及其预测因素仍然未知。我们在此报告一例致命的 HPD 病例，患者是一名 50 岁的转移性膀胱癌患者。他通过化放疗获得了完全反应（CR），随后接受了 12 个周期的化疗，CR 维持了 24 个月。在开始维持使用 PD-L1 抑制剂阿维列单抗三周后，出现了大量转移，导致患者死亡。利用即时尸检获得的转移组织进行的垚物分析表明，M2巨噬细胞、TGF-β信号传导和白细胞介素-8对HPD的发病机制起着重要作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

NPJ Precision Oncology ONCOLOGY-

CiteScore

9.90

自引率

1.30%

发文量

审稿时长

18 weeks

期刊介绍： Online-only and open access, npj Precision Oncology is an international, peer-reviewed journal dedicated to showcasing cutting-edge scientific research in all facets of precision oncology, spanning from fundamental science to translational applications and clinical medicine.