Nishimura Kazuki, Takahara Kiyoshi, Komura Kazumasa, Ishida Mitsuaki, Hirosuna Kensuke, Maenosono Ryoichi, Ajiro Masahiko, Sakamoto Moritoshi, Iwatsuki Kengo, Nakajima Yuki, Tsujino Takuya, Taniguchi Kohei, Tanaka Tomohito, Inamoto Teruo, Hirose Yoshinobu, Ono Fumihito, Kondo Yoichi, Yoshimi Akihide, Azuma Haruhito
Department of Urology, Osaka Medical and Pharmaceutical University, Takatsuki City, Osaka, Japan.
Division of Cancer RNA Research, National Cancer Center Research Institute, Chuo-Ku, Tokyo, Japan.
NPJ Precis Oncol. 2024 Sep 17;8(1):206. doi: 10.1038/s41698-024-00707-6.
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.
超进展性疾病（HPD）是一种自相矛盾的现象，其特征是在接受免疫检查点抑制剂治疗后肿瘤生长加速。然而，其致病因果关系及其预测因素仍不清楚。我们在此报告一例50岁转移性膀胱癌男性患者发生HPD的致死病例。他通过放化疗联合十二个周期的化疗实现了完全缓解（CR），并维持CR状态24个月。在开始维持使用PD-L1抑制剂阿维鲁单抗三周后，出现大量转移灶，导致患者死亡。利用尸检即刻获取的转移组织进行的组学分析表明，M2巨噬细胞、转化生长因子-β信号传导和白细胞介素-8在HPD发病机制中发挥了作用。
