ArticlemedRxiv : the preprint server for health sciences2025
Genomic and molecular associations with preoperative immune checkpoint inhibition in patients with stage III clear cell renal cell carcinoma.
Article in medRxiv : the preprint server for health sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02210117 (A Pilot Randomized Tissue-Based Study Evaluating Anti-PD1 Antibody or Anti-PD1 + Bevacizumab or Anti-PD1 + Anti-CTLA-4 in Patients With Metastatic Renal Cell Carcinoma Who Are Eligible for Cytoreductive Nephrectomy, Metastasectomy or Post-Treatment Biopsy), which is not on this map. Not yet cited in PubMed.
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A Pilot Randomized Tissue-Based Study Evaluating Anti-PD1 Antibody or Anti-PD1 + Bevacizumab or Anti-PD1 + Anti-CTLA-4 in Patients With Metastatic Renal Cell Carcinoma Who Are Eligible for Cytoreductive Nephrectomy, Metastasectomy or Post-Treatment Biopsy
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Abstract
Purpose: Patients with stage III clear cell renal cell carcinoma are at high risk for recurrence after nephrectomy. To mitigate overtreatment, there is a pressing clinical need to determine which patients benefit most from perioperative immune checkpoint inhibition. We performed a multimodal digital spatial analysis of gene and protein expression in stage III primary renal cell carcinomas, a subset of which had preoperative immune checkpoint inhibition exposure. Materials and Methods: Surgically resected tumors from stage III clear cell renal cell carcinoma patients were analyzed using the Nanostring GeoMx Digital Spatial Profiler. Differential expression analysis was performed and validated using NCT02210117 trial data to identify genes associated with immune checkpoint blockade and clinical response. A gene score was then generated to predict overall survival in patients from The Cancer Genome Atlas. Results: Among 19 patients, RNA expression significantly differed based on preoperative immune checkpoint blockade and recurrence - CD8+ effector and central-memory T-cell signatures were less prevalent in the treatment-naïve with recurrence group. Three out of four patients with preoperative immune checkpoint inhibition had recurrence. External validation yielded a 4-gene set ( Discussion: Preoperative immune checkpoint blockade favorably altered the tumor microenvironment to resemble that of treatment-naïve patients without recurrence. However, this did not translate to better clinical outcomes. On external validation, the genes
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