GEOTranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE333530GEOGSEfalseCD40 agonism in renal cell carcinoma enhances immune checkpoint activity through myeloid cellsImmune checkpoint blockade (ICB) has improved survival for patients with metastatic renal cell carcinoma (RCC) but there remains a need to overcome resistance mechanisms. CD40 agonists increase anti-tumoral immunity, but limited data are available on their activity in RCC. We evaluated CD40 agonism in combination with ICB in preclinical RCC models. Adding CD40 agonism to anti-CTLA-4, but not anti-PD1, improved survival in Renca-bearing mice. CD40 agonism and anti-CTLA-4 upregulated CCL2, increased intra-tumoral macrophages and type 1 conventional dendritic cells (cDC1), whereas polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) decreased compared to control. Neutralizing CCL2 with CD40 agonism and CTLA-4 blockade partially abrogated the anti-tumoral effect and led to less increase of cDC1 and less decrease of PMN-MDSCs populations. Our studies suggest that CCL2 at least partially mediates the anti-tumoral effects of CD40 agonism, and more importantly, that the addition of CD40 agonism to ICB, particularly anti-CTLA-4, might be beneficial in RCC.2026/06/02GSE333530GSM9767746GSM9767745GSM9767748GSM9767747GSM976774924247333530Mus musculus