Immune checkpoint inhibitors plus debulking surgery for patients with metastatic renal cell carcinoma: clinical outcomes and immunological correlates of a prospective pilot trial
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.
Authors
- Kamran Ahrar (ORCID: https://orcid.org/0000-0002-7800-2300)
- Li Zhao (ORCID: https://orcid.org/0000-0001-7374-3348)
- Matthew T. Campbell (ORCID: https://orcid.org/0000-0003-1915-4491)
- Marc Macaluso
- Rebecca S. Tidwell (ORCID: https://orcid.org/0000-0003-3041-8582)
- Alexsandra Espejo (ORCID: https://orcid.org/0000-0002-8841-7219)
- Shalini S. Yadav (ORCID: https://orcid.org/0000-0001-8266-5548)
- Alexandro E. Trevino (ORCID: https://orcid.org/0000-0002-9763-1540)
- Linghua Wang (ORCID: https://orcid.org/0000-0001-9380-0266)
- Sangeeta Goswami (ORCID: https://orcid.org/0000-0001-9201-4503)
- Aaron T. Mayer (ORCID: https://orcid.org/0000-0001-6429-0420)
- Sonali Jindal (ORCID: https://orcid.org/0000-0002-3911-6815)
- Priya Rao (ORCID: https://orcid.org/0000-0001-5672-0961)
- Nizar M. Tannir (ORCID: https://orcid.org/0000-0001-5559-8060)
- P. Andrew Futreal (ORCID: https://orcid.org/0000-0001-8663-2671)
- Yu Shen
- Jianjun Gao (ORCID: https://orcid.org/0000-0001-6138-4472)
- Padmanee Sharma (ORCID: https://orcid.org/0000-0003-4658-055X)
- José A. Karam (ORCID: https://orcid.org/0000-0001-7697-9591)
- Sreyashi Basu (ORCID: https://orcid.org/0000-0002-5028-3833)
- Wenbin Liu (ORCID: https://orcid.org/0000-0002-9080-8040)
- Jianhua Zhang (ORCID: https://orcid.org/0000-0001-5412-9860)
- Yulong Chen (ORCID: https://orcid.org/0009-0003-1436-9300)
- Zhong He (ORCID: https://orcid.org/0000-0002-7369-9989)
- Daniel D. Shapiro
- Christian Seua
- Ying Wang (ORCID: https://orcid.org/0000-0001-6638-8026)
Institutions
- The University of Texas MD Anderson Cancer Center (US)
- Menlo School (US)
- Enable Biosciences (United States) (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-02-21
- DOI
- https://doi.org/10.1038/s41467-025-57009-z
- Citations
- 11
- Primary Topic
- Renal cell carcinoma treatment
- Type
- article
- Field-Weighted Citation Impact
- 16.70
Funders
- Cancer Research Institute
- Andrew Sabin Family Foundation
- Parker Institute for Cancer Immunotherapy
- National Institutes of Health
- University of Texas MD Anderson Cancer Center
- National Cancer Institute