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.
Nature communications. 2025 Feb 21*** epublish ***
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
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., James P. Allison Institute, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Enable Medicine, Menlo Park, CA, USA., Immunotherapy Platform, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. .