Mechanistic insights into lethal hyper progressive disease induced by PD-L1 inhibitor in metastatic urothelial carcinoma
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.
Authors
- Kiyoshi Takahara (ORCID: https://orcid.org/0000-0002-4766-2074)
- Takuya Tsujino (ORCID: https://orcid.org/0000-0003-1559-1889)
- Tomohito Tanaka (ORCID: https://orcid.org/0000-0003-4210-701X)
- Kensuke Hirosuna (ORCID: https://orcid.org/0000-0002-9263-4929)
- Ryoichi Maenosono (ORCID: https://orcid.org/0000-0002-9045-5484)
- Yoshinobu Hirose (ORCID: https://orcid.org/0000-0002-3860-0293)
- Haruhito Azuma (ORCID: https://orcid.org/0000-0001-5497-1679)
- Kazuki Nishimura (ORCID: https://orcid.org/0000-0002-2878-7664)
- Kohei Taniguchi (ORCID: https://orcid.org/0000-0003-0648-1370)
- Fumihito Ono (ORCID: https://orcid.org/0000-0001-7532-5262)
- Teruo Inamoto (ORCID: https://orcid.org/0000-0002-1351-1315)
- Akihide Yoshimi (ORCID: https://orcid.org/0000-0002-0664-7281)
- Yoichi Kondo (ORCID: https://orcid.org/0000-0002-5036-6591)
- Kazumasa Komura (ORCID: https://orcid.org/0000-0003-4157-1929)
- Yuki Nakajima
- Mitsuaki Ishida
- Masahiko Ajiro (ORCID: https://orcid.org/0000-0002-7079-4788)
- Moritoshi Sakamoto (ORCID: https://orcid.org/0009-0000-2053-0058)
- Kengo Iwatsuki
Institutions
- Fujita Health University (JP)
- Okayama University (JP)
- National Cancer Research Institute (GB)
- Osaka University of Pharmaceutical Sciences (JP)
Publication Details
- Journal
- npj Precision Oncology
- Published
- 2024-09-17
- DOI
- https://doi.org/10.1038/s41698-024-00707-6
- Citations
- 2
- Primary Topic
- Bladder and Urothelial Cancer Treatments
- Type
- article
- Field-Weighted Citation Impact
- 1.15
Funders
- Naito Foundation
- Takeda Science Foundation
- Japan Agency for Medical Research and Development
- Japanese Urological Association
- Japan Society for the Promotion of Science