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

Bibliographic Details
Title: Immune checkpoint inhibitors plus debulking surgery for patients with metastatic renal cell carcinoma: clinical outcomes and immunological correlates of a prospective pilot trial
Authors: 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
Source: Nature Communications, Vol 16, Iss 1, Pp 1-13 (2025)
Publisher Information: Nature Portfolio, 2025.
Publication Year: 2025
Collection: LCC:Science
Subject Terms: Science
More Details: 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.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2041-1723
Relation: https://doaj.org/toc/2041-1723
DOI: 10.1038/s41467-025-57009-z
Access URL: https://doaj.org/article/5e3b63f2a86245c78d3f9795ad38913d
Accession Number: edsdoj.5e3b63f2a86245c78d3f9795ad38913d
Database: Directory of Open Access Journals
More Details
ISSN:20411723
DOI:10.1038/s41467-025-57009-z
Published in:Nature Communications
Language:English