From clinical observations to molecular insights: Decoding immune checkpoint inhibitors‐induced prostatitis
Abstract Immune checkpoint inhibitors (ICIs) have dramatically transformed cancer treatment; however, their impact on the male reproductive system remains poorly understood. This study aims to elucidate the incidence, risk factors, and molecular mechanisms underlying ICI‐associated prostatitis. We c...
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Wiley
2025-06-01
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| Online Access: | https://doi.org/10.1002/VIW.20240113 |
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| author | Peng Luo Ying Liu Lan Xu Zaoqu Liu Linhui Wang Hank Z. H. Wong Quan Cheng Anqi Lin Xiao Fang Aimin Jiang |
| author_facet | Peng Luo Ying Liu Lan Xu Zaoqu Liu Linhui Wang Hank Z. H. Wong Quan Cheng Anqi Lin Xiao Fang Aimin Jiang |
| author_sort | Peng Luo |
| collection | DOAJ |
| description | Abstract Immune checkpoint inhibitors (ICIs) have dramatically transformed cancer treatment; however, their impact on the male reproductive system remains poorly understood. This study aims to elucidate the incidence, risk factors, and molecular mechanisms underlying ICI‐associated prostatitis. We conducted an analysis of ICI‐associated prostatitis utilizing the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database and evaluated risk through the application of the reporting odds ratio. A mouse model of ICI treatment was developed, and subsequent transcriptomic changes in prostate tissue were investigated using high‐throughput sequencing. Hematoxylin and eosin staining, immunohistochemistry, Von Frey testing, and enzyme‐linked immunosorbent assay were employed to confirm ICI‐induced prostatitis and further delineate its underlying mechanisms. Additionally, we investigated the therapeutic potential of specifically targeting interleukin‐6 (IL‐6) and extracellular signal‐regulated kinase (ERK) signaling pathways. FAERS analysis demonstrated a statistically significant positive correlation between ICI treatment and prostatitis risk (p < .05). In the murine model, ICI treatment induced an elevated inflammatory response in prostate tissue, characterized by enhanced inflammatory cell infiltration and upregulated expression of IL‐6 and tumor necrosis factor‐alpha. Transcriptomic analysis revealed significant activation of multiple inflammation‐related signaling pathways in prostate tissue following ICI treatment (false discovery rate < 0.05). Targeted inhibition of IL‐6 or ERK signaling pathways significantly attenuated ICI‐induced prostatitis symptoms, resulting in improved tissue pathology and decreased inflammatory factor expression (p < .01). This study delineates the characteristics and potential molecular mechanisms underlying ICI‐associated prostatitis, thereby establishing a theoretical foundation for the development of prevention and treatment strategies. Targeted modulation of IL‐6 and ERK signaling pathways may present novel therapeutic interventions for ICI‐associated prostatitis, thus warranting further clinical validation. |
| format | Article |
| id | doaj-art-853952f7c67140fea3ef68afe0160d20 |
| institution | Kabale University |
| issn | 2688-3988 2688-268X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
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| spelling | doaj-art-853952f7c67140fea3ef68afe0160d202025-08-20T03:31:07ZengWileyView2688-39882688-268X2025-06-0163n/an/a10.1002/VIW.20240113From clinical observations to molecular insights: Decoding immune checkpoint inhibitors‐induced prostatitisPeng Luo0Ying Liu1Lan Xu2Zaoqu Liu3Linhui Wang4Hank Z. H. Wong5Quan Cheng6Anqi Lin7Xiao Fang8Aimin Jiang9Donghai County People's Hospital ‐ Jiangnan University Smart Healthcare Joint Laboratory Donghai County People's Hospital (Affiliated Kangda College of Nanjing Medical University) Lianyungang ChinaDepartment of Urology, Changhai Hospital Naval Medical University (Second Military Medical University) Shanghai ChinaDepartment of Oncology Zhujiang Hospital Southern Medical University Guangzhou ChinaInstitute of Basic Medical Sciences Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Urology, Changhai Hospital Naval Medical University (Second Military Medical University) Shanghai ChinaLi Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong SAR ChinaDepartment of Neurosurgery Xiangya Hospital Central South University Changsha ChinaDonghai County People's Hospital ‐ Jiangnan University Smart Healthcare Joint Laboratory Donghai County People's Hospital (Affiliated Kangda College of Nanjing Medical University) Lianyungang ChinaDepartment of Urology, Changzheng Hospital Naval Medical University (Second Military Medical University) Shanghai ChinaDepartment of Urology, Changzheng Hospital Naval Medical University (Second Military Medical University) Shanghai ChinaAbstract Immune checkpoint inhibitors (ICIs) have dramatically transformed cancer treatment; however, their impact on the male reproductive system remains poorly understood. This study aims to elucidate the incidence, risk factors, and molecular mechanisms underlying ICI‐associated prostatitis. We conducted an analysis of ICI‐associated prostatitis utilizing the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database and evaluated risk through the application of the reporting odds ratio. A mouse model of ICI treatment was developed, and subsequent transcriptomic changes in prostate tissue were investigated using high‐throughput sequencing. Hematoxylin and eosin staining, immunohistochemistry, Von Frey testing, and enzyme‐linked immunosorbent assay were employed to confirm ICI‐induced prostatitis and further delineate its underlying mechanisms. Additionally, we investigated the therapeutic potential of specifically targeting interleukin‐6 (IL‐6) and extracellular signal‐regulated kinase (ERK) signaling pathways. FAERS analysis demonstrated a statistically significant positive correlation between ICI treatment and prostatitis risk (p < .05). In the murine model, ICI treatment induced an elevated inflammatory response in prostate tissue, characterized by enhanced inflammatory cell infiltration and upregulated expression of IL‐6 and tumor necrosis factor‐alpha. Transcriptomic analysis revealed significant activation of multiple inflammation‐related signaling pathways in prostate tissue following ICI treatment (false discovery rate < 0.05). Targeted inhibition of IL‐6 or ERK signaling pathways significantly attenuated ICI‐induced prostatitis symptoms, resulting in improved tissue pathology and decreased inflammatory factor expression (p < .01). This study delineates the characteristics and potential molecular mechanisms underlying ICI‐associated prostatitis, thereby establishing a theoretical foundation for the development of prevention and treatment strategies. Targeted modulation of IL‐6 and ERK signaling pathways may present novel therapeutic interventions for ICI‐associated prostatitis, thus warranting further clinical validation.https://doi.org/10.1002/VIW.20240113FAERSICI‐associated prostatitisimmune checkpoint inhibitorsmolecular mechanismmurine model |
| spellingShingle | Peng Luo Ying Liu Lan Xu Zaoqu Liu Linhui Wang Hank Z. H. Wong Quan Cheng Anqi Lin Xiao Fang Aimin Jiang From clinical observations to molecular insights: Decoding immune checkpoint inhibitors‐induced prostatitis View FAERS ICI‐associated prostatitis immune checkpoint inhibitors molecular mechanism murine model |
| title | From clinical observations to molecular insights: Decoding immune checkpoint inhibitors‐induced prostatitis |
| title_full | From clinical observations to molecular insights: Decoding immune checkpoint inhibitors‐induced prostatitis |
| title_fullStr | From clinical observations to molecular insights: Decoding immune checkpoint inhibitors‐induced prostatitis |
| title_full_unstemmed | From clinical observations to molecular insights: Decoding immune checkpoint inhibitors‐induced prostatitis |
| title_short | From clinical observations to molecular insights: Decoding immune checkpoint inhibitors‐induced prostatitis |
| title_sort | from clinical observations to molecular insights decoding immune checkpoint inhibitors induced prostatitis |
| topic | FAERS ICI‐associated prostatitis immune checkpoint inhibitors molecular mechanism murine model |
| url | https://doi.org/10.1002/VIW.20240113 |
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