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

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

doi:10.1038/s41698-024-00707-6

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

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

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	206
Journal	npj Precision Oncology
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41698-024-00707-6
Publication status	Published - 12-2024
Externally published	Yes

All Science Journal Classification (ASJC) codes

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41698-024-00707-6

Cite this

Nishimura, K., Takahara, K., Komura, K., Ishida, M., Hirosuna, K., Maenosono, R., Ajiro, M., Sakamoto, M., Iwatsuki, K., Nakajima, Y., Tsujino, T., Taniguchi, K., Tanaka, T., Inamoto, T., Hirose, Y., Ono, F., Kondo, Y., Yoshimi, A., & Azuma, H. (2024). Mechanistic insights into lethal hyper progressive disease induced by PD-L1 inhibitor in metastatic urothelial carcinoma. npj Precision Oncology, 8(1), Article 206. https://doi.org/10.1038/s41698-024-00707-6

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

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{\textquoteright}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.",

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

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

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doi = "10.1038/s41698-024-00707-6",

language = "English",

volume = "8",

journal = "npj Precision Oncology",

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Nishimura, K, Takahara, K, Komura, K, Ishida, M, Hirosuna, K, Maenosono, R, Ajiro, M, Sakamoto, M, Iwatsuki, K, Nakajima, Y, Tsujino, T, Taniguchi, K, Tanaka, T, Inamoto, T, Hirose, Y, Ono, F, Kondo, Y, Yoshimi, A & Azuma, H 2024, 'Mechanistic insights into lethal hyper progressive disease induced by PD-L1 inhibitor in metastatic urothelial carcinoma', npj Precision Oncology, vol. 8, no. 1, 206. https://doi.org/10.1038/s41698-024-00707-6

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T1 - Mechanistic insights into lethal hyper progressive disease induced by PD-L1 inhibitor in metastatic urothelial carcinoma

AU - Nishimura, Kazuki

AU - Takahara, Kiyoshi

AU - Komura, Kazumasa

AU - Ishida, Mitsuaki

AU - Hirosuna, Kensuke

AU - Maenosono, Ryoichi

AU - Ajiro, Masahiko

AU - Sakamoto, Moritoshi

AU - Iwatsuki, Kengo

AU - Nakajima, Yuki

AU - Tsujino, Takuya

AU - Taniguchi, Kohei

AU - Tanaka, Tomohito

AU - Inamoto, Teruo

AU - Hirose, Yoshinobu

AU - Ono, Fumihito

AU - Kondo, Yoichi

AU - Yoshimi, Akihide

AU - Azuma, Haruhito

PY - 2024/12

Y1 - 2024/12

N2 - 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.

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

Abstract

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