Immune checkpoint inhibitors plus debulking surgery for patients with metastatic renal cell carcinoma: clinical outcomes and immunological correlates of a prospective pilot trial

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 and Padmanee Sharma (padsharma@mdanderson.org)
Additional contact information
Sangeeta Goswami: The University of Texas MD Anderson Cancer Center
Jianjun Gao: The University of Texas MD Anderson Cancer Center
Sreyashi Basu: The University of Texas MD Anderson Cancer Center
Daniel D. Shapiro: The University of Texas MD Anderson Cancer Center
Jose A. Karam: The University of Texas MD Anderson Cancer Center
Rebecca Slack Tidwell: The University of Texas MD Anderson Cancer Center
Kamran Ahrar: The University of Texas MD Anderson Cancer Center
Matthew T. Campbell: The University of Texas MD Anderson Cancer Center
Yu Shen: The University of Texas MD Anderson Cancer Center
Alexandro E. Trevino: Enable Medicine
Aaron T. Mayer: Enable Medicine
Alexsandra B. Espejo: The University of Texas MD Anderson Cancer Center
Christian Seua: The University of Texas MD Anderson Cancer Center
Marc D. Macaluso: The University of Texas MD Anderson Cancer Center
Yulong Chen: The University of Texas MD Anderson Cancer Center
Wenbin Liu: The University of Texas MD Anderson Cancer Center
Zhong He: The University of Texas MD Anderson Cancer Center
Shalini S. Yadav: The University of Texas MD Anderson Cancer Center
Ying Wang: The University of Texas MD Anderson Cancer Center
Priya Rao: The University of Texas MD Anderson Cancer Center
Li Zhao: The University of Texas MD Anderson Cancer Center
Jianhua Zhang: The University of Texas MD Anderson Cancer Center
Sonali Jindal: The University of Texas MD Anderson Cancer Center
Nizar M. Tannir: The University of Texas MD Anderson Cancer Center
Andrew Futreal: The University of Texas MD Anderson Cancer Center
Linghua Wang: The University of Texas MD Anderson Cancer Center
Padmanee Sharma: The University of Texas MD Anderson Cancer Center

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-57009-z

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