Association of 5α-reductase inhibitor prescription with immunotherapy efficacy in metastatic renal cell carcinoma: a multicenter retrospective analysis
Background Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of metastatic renal cell carcinoma (mRCC), but response rates remain heterogeneous, and reliable predictive biomarkers are lacking. Recent studies suggest that androgen receptor (AR) signaling plays a role in regulating...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2025-02-01
|
| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/13/2/e011154.full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850096200476262400 |
|---|---|
| author | Lin Yang Hai Huang Qiong Wang Peng Wu Ke Chen Weijia Li Bisheng Cheng Jilin Wu Jianghua Yang WenTai Shangguan Wenxue Huang Cunzhen Ma Zhuohang Li Boyuan Sun |
| author_facet | Lin Yang Hai Huang Qiong Wang Peng Wu Ke Chen Weijia Li Bisheng Cheng Jilin Wu Jianghua Yang WenTai Shangguan Wenxue Huang Cunzhen Ma Zhuohang Li Boyuan Sun |
| author_sort | Lin Yang |
| collection | DOAJ |
| description | Background Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of metastatic renal cell carcinoma (mRCC), but response rates remain heterogeneous, and reliable predictive biomarkers are lacking. Recent studies suggest that androgen receptor (AR) signaling plays a role in regulating CD8+ T-cell function, implying that 5α-reductase inhibitors (5-ARIs), which lower androgen activity, could enhance antitumor immunity and improve clinical outcomes in patients receiving immunotherapy. This study retrospectively investigates the impact of a history of 5-ARI use (≥12 months) on the efficacy of ICIs in mRCC.Methods We conducted a multicenter retrospective cohort study of 185 patients with mRCC who received ICIs. Patients were stratified based on their history of 5-ARI use. Baseline characteristics included age, body mass index, International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk group, programmed death-ligand 1 (PD-L1) expression levels, tumor stage, and metastasis sites. The primary endpoints were progression-free survival (PFS) and overall survival (OS), analyzed using Cox proportional hazards models. Secondary endpoints included objective response rate (ORR) and disease control rate (DCR). Key immunological insights were gained through single-cell RNA sequencing analysis of tumor samples.Results Patients with a history of 5-ARI use demonstrated improved ORR (59.8% vs 39.8%, p=0.0075) and DCR (87.0% vs 78.7%, p=0.1747) compared with those without. The median PFS and OS were significantly longer in the 5-ARI group, with HRs of 0.64 (95% CI: 0.47 to 0.86, p=0.0085) for PFS and 0.65 (95% CI: 0.47 to 0.90, p=0.0271) for OS. Subgroup analysis further indicated enhanced ICI efficacy with 5-ARI use across age, IMDC risk scores, and PD-L1 expression levels. Single-cell RNA sequencing analysis revealed that 5-ARI treated patients exhibited a reduced presence of regulatory T cells and CD8 T-cell exhaustion (CD8 Tex), and lower programmed cell death protein-1 expression in CD8 Tex cells, suggesting an immunologically favorable modification of the tumor.Conclusion A history of 5-ARI use is associated with improved responses to ICI therapy in mRCC, potentially through AR-related modulation of CD8+ T-cell activity and favorable alterations in the immune microenvironment. These findings support further investigation into androgen-targeted approaches as adjunctive strategies in immunotherapy for RCC. |
| format | Article |
| id | doaj-art-bc21ed4148704ad2addb02ce6b6565d5 |
| institution | DOAJ |
| issn | 2051-1426 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-bc21ed4148704ad2addb02ce6b6565d52025-08-20T02:41:17ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262025-02-0113210.1136/jitc-2024-011154Association of 5α-reductase inhibitor prescription with immunotherapy efficacy in metastatic renal cell carcinoma: a multicenter retrospective analysisLin Yang0Hai Huang1Qiong Wang2Peng Wu3Ke Chen4Weijia Li5Bisheng Cheng6Jilin Wu7Jianghua Yang8WenTai Shangguan9Wenxue Huang10Cunzhen Ma11Zhuohang Li12Boyuan Sun134 Department of Urology, Southern Medical University, Guangzhou, Guangdong, China6 Department of Urology, Sun Yat-sen Memorial Hospital, Guangzhou, Guangdong, China4 Department of Urology, Southern Medical University, Guangzhou, Guangdong, China7 Southern Medical University Nanfang Hospital, Guangzhou, Guangdong, China3 Shenzhen People’s Hospital, Shenzhen, Guangdong, China4 Department of Urology, Southern Medical University, Guangzhou, Guangdong, China1 Department of Urology, Southern Medical University Nanfang Hospital, Guangzhou, Guangdong, China2 Department of Urology, Peking University People’s Hospital, Beijing, Beijing, China5 Department of Urology, Sun Yat-sen University, Guangzhou, Guangdong, China4 Department of Urology, Southern Medical University, Guangzhou, Guangdong, China5 Department of Urology, Sun Yat-sen University, Guangzhou, Guangdong, China4 Department of Urology, Southern Medical University, Guangzhou, Guangdong, China4 Department of Urology, Southern Medical University, Guangzhou, Guangdong, China4 Department of Urology, Southern Medical University, Guangzhou, Guangdong, ChinaBackground Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of metastatic renal cell carcinoma (mRCC), but response rates remain heterogeneous, and reliable predictive biomarkers are lacking. Recent studies suggest that androgen receptor (AR) signaling plays a role in regulating CD8+ T-cell function, implying that 5α-reductase inhibitors (5-ARIs), which lower androgen activity, could enhance antitumor immunity and improve clinical outcomes in patients receiving immunotherapy. This study retrospectively investigates the impact of a history of 5-ARI use (≥12 months) on the efficacy of ICIs in mRCC.Methods We conducted a multicenter retrospective cohort study of 185 patients with mRCC who received ICIs. Patients were stratified based on their history of 5-ARI use. Baseline characteristics included age, body mass index, International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk group, programmed death-ligand 1 (PD-L1) expression levels, tumor stage, and metastasis sites. The primary endpoints were progression-free survival (PFS) and overall survival (OS), analyzed using Cox proportional hazards models. Secondary endpoints included objective response rate (ORR) and disease control rate (DCR). Key immunological insights were gained through single-cell RNA sequencing analysis of tumor samples.Results Patients with a history of 5-ARI use demonstrated improved ORR (59.8% vs 39.8%, p=0.0075) and DCR (87.0% vs 78.7%, p=0.1747) compared with those without. The median PFS and OS were significantly longer in the 5-ARI group, with HRs of 0.64 (95% CI: 0.47 to 0.86, p=0.0085) for PFS and 0.65 (95% CI: 0.47 to 0.90, p=0.0271) for OS. Subgroup analysis further indicated enhanced ICI efficacy with 5-ARI use across age, IMDC risk scores, and PD-L1 expression levels. Single-cell RNA sequencing analysis revealed that 5-ARI treated patients exhibited a reduced presence of regulatory T cells and CD8 T-cell exhaustion (CD8 Tex), and lower programmed cell death protein-1 expression in CD8 Tex cells, suggesting an immunologically favorable modification of the tumor.Conclusion A history of 5-ARI use is associated with improved responses to ICI therapy in mRCC, potentially through AR-related modulation of CD8+ T-cell activity and favorable alterations in the immune microenvironment. These findings support further investigation into androgen-targeted approaches as adjunctive strategies in immunotherapy for RCC.https://jitc.bmj.com/content/13/2/e011154.full |
| spellingShingle | Lin Yang Hai Huang Qiong Wang Peng Wu Ke Chen Weijia Li Bisheng Cheng Jilin Wu Jianghua Yang WenTai Shangguan Wenxue Huang Cunzhen Ma Zhuohang Li Boyuan Sun Association of 5α-reductase inhibitor prescription with immunotherapy efficacy in metastatic renal cell carcinoma: a multicenter retrospective analysis Journal for ImmunoTherapy of Cancer |
| title | Association of 5α-reductase inhibitor prescription with immunotherapy efficacy in metastatic renal cell carcinoma: a multicenter retrospective analysis |
| title_full | Association of 5α-reductase inhibitor prescription with immunotherapy efficacy in metastatic renal cell carcinoma: a multicenter retrospective analysis |
| title_fullStr | Association of 5α-reductase inhibitor prescription with immunotherapy efficacy in metastatic renal cell carcinoma: a multicenter retrospective analysis |
| title_full_unstemmed | Association of 5α-reductase inhibitor prescription with immunotherapy efficacy in metastatic renal cell carcinoma: a multicenter retrospective analysis |
| title_short | Association of 5α-reductase inhibitor prescription with immunotherapy efficacy in metastatic renal cell carcinoma: a multicenter retrospective analysis |
| title_sort | association of 5α reductase inhibitor prescription with immunotherapy efficacy in metastatic renal cell carcinoma a multicenter retrospective analysis |
| url | https://jitc.bmj.com/content/13/2/e011154.full |
| work_keys_str_mv | AT linyang associationof5areductaseinhibitorprescriptionwithimmunotherapyefficacyinmetastaticrenalcellcarcinomaamulticenterretrospectiveanalysis AT haihuang associationof5areductaseinhibitorprescriptionwithimmunotherapyefficacyinmetastaticrenalcellcarcinomaamulticenterretrospectiveanalysis AT qiongwang associationof5areductaseinhibitorprescriptionwithimmunotherapyefficacyinmetastaticrenalcellcarcinomaamulticenterretrospectiveanalysis AT pengwu associationof5areductaseinhibitorprescriptionwithimmunotherapyefficacyinmetastaticrenalcellcarcinomaamulticenterretrospectiveanalysis AT kechen associationof5areductaseinhibitorprescriptionwithimmunotherapyefficacyinmetastaticrenalcellcarcinomaamulticenterretrospectiveanalysis AT weijiali associationof5areductaseinhibitorprescriptionwithimmunotherapyefficacyinmetastaticrenalcellcarcinomaamulticenterretrospectiveanalysis AT bishengcheng associationof5areductaseinhibitorprescriptionwithimmunotherapyefficacyinmetastaticrenalcellcarcinomaamulticenterretrospectiveanalysis AT jilinwu associationof5areductaseinhibitorprescriptionwithimmunotherapyefficacyinmetastaticrenalcellcarcinomaamulticenterretrospectiveanalysis AT jianghuayang associationof5areductaseinhibitorprescriptionwithimmunotherapyefficacyinmetastaticrenalcellcarcinomaamulticenterretrospectiveanalysis AT wentaishangguan associationof5areductaseinhibitorprescriptionwithimmunotherapyefficacyinmetastaticrenalcellcarcinomaamulticenterretrospectiveanalysis AT wenxuehuang associationof5areductaseinhibitorprescriptionwithimmunotherapyefficacyinmetastaticrenalcellcarcinomaamulticenterretrospectiveanalysis AT cunzhenma associationof5areductaseinhibitorprescriptionwithimmunotherapyefficacyinmetastaticrenalcellcarcinomaamulticenterretrospectiveanalysis AT zhuohangli associationof5areductaseinhibitorprescriptionwithimmunotherapyefficacyinmetastaticrenalcellcarcinomaamulticenterretrospectiveanalysis AT boyuansun associationof5areductaseinhibitorprescriptionwithimmunotherapyefficacyinmetastaticrenalcellcarcinomaamulticenterretrospectiveanalysis |