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Immunomodulatory response to neoadjuvant nivolumab in non-metastatic clear cell renal cell carcinoma.
Singla, Nirmish; Nirschl, Thomas R; Obradovic, Aleksandar Z; Shenderov, Eugene; Lombardo, Kara; Liu, Xiaopu; Pons, Alice; Zarif, Jelani C; Rowe, Steven P; Trock, Bruce J; Hammers, Hans J; Bivalacqua, Trinity J; Pierorazio, Phillip M; Deutsch, Julie S; Lotan, Tamara L; Taube, Janis M; Ged, Yasser M A; Gorin, Michael A; Allaf, Mohamad E; Drake, Charles G.
Affiliation
  • Singla N; Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Park 213, Baltimore, MD, 21287, USA. nsingla2@jhmi.edu.
  • Nirschl TR; Department of Oncology, Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA. nsingla2@jhmi.edu.
  • Obradovic AZ; Department of Oncology, Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
  • Shenderov E; Pathobiology Graduate Program, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Lombardo K; Bloomberg~Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Liu X; Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.
  • Pons A; Department of Oncology, Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
  • Zarif JC; Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Park 213, Baltimore, MD, 21287, USA.
  • Rowe SP; Department of Oncology, Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
  • Trock BJ; Department of Oncology, Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
  • Hammers HJ; Department of Oncology, Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
  • Bivalacqua TJ; Bloomberg~Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Pierorazio PM; The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Deutsch JS; Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Park 213, Baltimore, MD, 21287, USA.
  • Lotan TL; Division of Hematology/Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Taube JM; Division of Urology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
  • Ged YMA; Division of Urology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
  • Gorin MA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Allaf ME; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Drake CG; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Sci Rep ; 14(1): 1458, 2024 01 17.
Article in En | MEDLINE | ID: mdl-38228729
ABSTRACT
Novel perioperative strategies are needed to reduce recurrence rates in patients undergoing nephrectomy for high-risk, non-metastatic clear cell renal cell carcinoma (ccRCC). We conducted a prospective, phase I trial of neoadjuvant nivolumab prior to nephrectomy in 15 evaluable patients with non-metastatic ccRCC. We leveraged tissue from that cohort to elucidate the effects of PD-1 inhibition on immune cell populations in ccRCC and correlate the evolving immune milieu with anti-PD-1 response. We found that nivolumab durably induces a pro-inflammatory state within the primary tumor, and baseline immune infiltration within the primary tumor correlates with nivolumab responsiveness. Nivolumab increases CTLA-4 expression in the primary tumor, and subsequent nephrectomy increases circulating concentrations of sPD-L1, sPD-L3 (sB7-H3), and s4-1BB. These findings form the basis to consider neoadjuvant immune checkpoint inhibition (ICI) for high-risk ccRCC while the tumor remains in situ and provide the rationale for perioperative strategies of novel ICI combinations.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Carcinoma, Renal Cell / Kidney Neoplasms Type of study: Observational_studies / Risk_factors_studies Limits: Humans Language: En Journal: Sci Rep Year: 2024 Document type: Article Affiliation country:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Carcinoma, Renal Cell / Kidney Neoplasms Type of study: Observational_studies / Risk_factors_studies Limits: Humans Language: En Journal: Sci Rep Year: 2024 Document type: Article Affiliation country: