Immune checkpoint inhibitors plus debulking surgery for patients with metastatic renal cell carcinoma: clinical outcomes and immunological correlates of a prospective pilot trial
Abstract Surgical removal of primary tumors reverses tumor-mediated immune suppression in pre-clinical models with metastatic disease. However, how cytoreductive surgery in the metastatic setting modulates the immune responses in patients, especially in the context of immune checkpoint therapy (ICT)...
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-57009-z |
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| author | Sangeeta Goswami Jianjun Gao Sreyashi Basu Daniel D. Shapiro Jose A. Karam Rebecca Slack Tidwell Kamran Ahrar Matthew T. Campbell Yu Shen Alexandro E. Trevino Aaron T. Mayer Alexsandra B. Espejo Christian Seua Marc D. Macaluso Yulong Chen Wenbin Liu Zhong He Shalini S. Yadav Ying Wang Priya Rao Li Zhao Jianhua Zhang Sonali Jindal Nizar M. Tannir Andrew Futreal Linghua Wang Padmanee Sharma |
| author_facet | Sangeeta Goswami Jianjun Gao Sreyashi Basu Daniel D. Shapiro Jose A. Karam Rebecca Slack Tidwell Kamran Ahrar Matthew T. Campbell Yu Shen Alexandro E. Trevino Aaron T. Mayer Alexsandra B. Espejo Christian Seua Marc D. Macaluso Yulong Chen Wenbin Liu Zhong He Shalini S. Yadav Ying Wang Priya Rao Li Zhao Jianhua Zhang Sonali Jindal Nizar M. Tannir Andrew Futreal Linghua Wang Padmanee Sharma |
| author_sort | Sangeeta Goswami |
| collection | DOAJ |
| description | Abstract Surgical removal of primary tumors reverses tumor-mediated immune suppression in pre-clinical models with metastatic disease. However, how cytoreductive surgery in the metastatic setting modulates the immune responses in patients, especially in the context of immune checkpoint therapy (ICT), is not understood. We report the first prospective, pilot, non-comparative clinical trial (NCT02210117) to evaluate the feasibility, clinical benefits, and immunologic changes of combining three different ICT-containing strategies with cytoreductive surgery or biopsy for patients with metastatic clear cell renal cell carcinoma. Primary safety endpoint of this trial has been met, with 43 patients completing cytoreductive surgery, 36 patients undergoing post-ICT biopsy, and 25 patients without either procedure due to progressive disease or toxicities or withdrawal of consent (total N = 104). Patients receiving ICT with cytoreductive surgery or biopsy, did not experience additional ICT- or procedure-related toxicities. The median overall survival was 54.7 months for patients who received ICT plus cytoreductive surgery. Immune-monitoring studies demonstrated that cytoreductive surgery increased antigen-presenting dendritic cell population and decreased KDM6B-expressing immune-suppressive myeloid cells in the peripheral blood. This study highlighted the feasibility of combining ICT with cytoreductive surgery in a metastatic setting and demonstrated the potential enhancement of immune responses following ICT plus cytoreductive surgery. |
| format | Article |
| id | doaj-art-5e3b63f2a86245c78d3f9795ad38913d |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-5e3b63f2a86245c78d3f9795ad38913d2025-08-20T03:13:14ZengNature PortfolioNature Communications2041-17232025-02-0116111310.1038/s41467-025-57009-zImmune checkpoint inhibitors plus debulking surgery for patients with metastatic renal cell carcinoma: clinical outcomes and immunological correlates of a prospective pilot trialSangeeta Goswami0Jianjun Gao1Sreyashi Basu2Daniel D. Shapiro3Jose A. Karam4Rebecca Slack Tidwell5Kamran Ahrar6Matthew T. Campbell7Yu Shen8Alexandro E. Trevino9Aaron T. Mayer10Alexsandra B. Espejo11Christian Seua12Marc D. Macaluso13Yulong Chen14Wenbin Liu15Zhong He16Shalini S. Yadav17Ying Wang18Priya Rao19Li Zhao20Jianhua Zhang21Sonali Jindal22Nizar M. Tannir23Andrew Futreal24Linghua Wang25Padmanee Sharma26Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer CenterDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer CenterJames P. Allison Institute, The University of Texas MD Anderson Cancer CenterDepartment of Urology, The University of Texas MD Anderson Cancer CenterDepartment of Urology, The University of Texas MD Anderson Cancer CenterDepartment of Biostatistics, The University of Texas MD Anderson Cancer CenterDepartment of Interventional Radiology, The University of Texas MD Anderson Cancer CenterDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer CenterDepartment of Biostatistics, The University of Texas MD Anderson Cancer CenterEnable MedicineEnable MedicineJames P. Allison Institute, The University of Texas MD Anderson Cancer CenterJames P. Allison Institute, The University of Texas MD Anderson Cancer CenterJames P. Allison Institute, The University of Texas MD Anderson Cancer CenterJames P. Allison Institute, The University of Texas MD Anderson Cancer CenterJames P. Allison Institute, The University of Texas MD Anderson Cancer CenterJames P. Allison Institute, The University of Texas MD Anderson Cancer CenterImmunotherapy Platform, The University of Texas MD Anderson Cancer CenterImmunotherapy Platform, The University of Texas MD Anderson Cancer CenterDepartment of Pathology, The University of Texas MD Anderson Cancer CenterDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer CenterDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer CenterJames P. Allison Institute, The University of Texas MD Anderson Cancer CenterDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer CenterDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer CenterJames P. Allison Institute, The University of Texas MD Anderson Cancer CenterDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer CenterAbstract Surgical removal of primary tumors reverses tumor-mediated immune suppression in pre-clinical models with metastatic disease. However, how cytoreductive surgery in the metastatic setting modulates the immune responses in patients, especially in the context of immune checkpoint therapy (ICT), is not understood. We report the first prospective, pilot, non-comparative clinical trial (NCT02210117) to evaluate the feasibility, clinical benefits, and immunologic changes of combining three different ICT-containing strategies with cytoreductive surgery or biopsy for patients with metastatic clear cell renal cell carcinoma. Primary safety endpoint of this trial has been met, with 43 patients completing cytoreductive surgery, 36 patients undergoing post-ICT biopsy, and 25 patients without either procedure due to progressive disease or toxicities or withdrawal of consent (total N = 104). Patients receiving ICT with cytoreductive surgery or biopsy, did not experience additional ICT- or procedure-related toxicities. The median overall survival was 54.7 months for patients who received ICT plus cytoreductive surgery. Immune-monitoring studies demonstrated that cytoreductive surgery increased antigen-presenting dendritic cell population and decreased KDM6B-expressing immune-suppressive myeloid cells in the peripheral blood. This study highlighted the feasibility of combining ICT with cytoreductive surgery in a metastatic setting and demonstrated the potential enhancement of immune responses following ICT plus cytoreductive surgery.https://doi.org/10.1038/s41467-025-57009-z |
| spellingShingle | Sangeeta Goswami Jianjun Gao Sreyashi Basu Daniel D. Shapiro Jose A. Karam Rebecca Slack Tidwell Kamran Ahrar Matthew T. Campbell Yu Shen Alexandro E. Trevino Aaron T. Mayer Alexsandra B. Espejo Christian Seua Marc D. Macaluso Yulong Chen Wenbin Liu Zhong He Shalini S. Yadav Ying Wang Priya Rao Li Zhao Jianhua Zhang Sonali Jindal Nizar M. Tannir Andrew Futreal Linghua Wang Padmanee Sharma Immune checkpoint inhibitors plus debulking surgery for patients with metastatic renal cell carcinoma: clinical outcomes and immunological correlates of a prospective pilot trial Nature Communications |
| title | Immune checkpoint inhibitors plus debulking surgery for patients with metastatic renal cell carcinoma: clinical outcomes and immunological correlates of a prospective pilot trial |
| title_full | Immune checkpoint inhibitors plus debulking surgery for patients with metastatic renal cell carcinoma: clinical outcomes and immunological correlates of a prospective pilot trial |
| title_fullStr | Immune checkpoint inhibitors plus debulking surgery for patients with metastatic renal cell carcinoma: clinical outcomes and immunological correlates of a prospective pilot trial |
| title_full_unstemmed | Immune checkpoint inhibitors plus debulking surgery for patients with metastatic renal cell carcinoma: clinical outcomes and immunological correlates of a prospective pilot trial |
| title_short | Immune checkpoint inhibitors plus debulking surgery for patients with metastatic renal cell carcinoma: clinical outcomes and immunological correlates of a prospective pilot trial |
| title_sort | immune checkpoint inhibitors plus debulking surgery for patients with metastatic renal cell carcinoma clinical outcomes and immunological correlates of a prospective pilot trial |
| url | https://doi.org/10.1038/s41467-025-57009-z |
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