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Omics · study · 2026

CD40 agonism in renal cell carcinoma enhances immune checkpoint activity through myeloid cells

Listed in NCBI GEO

Immune checkpoint blockade (ICB) has improved survival for patients with metastatic renal cell carcinoma (RCC) but there remains a need to overcome resistance mechanisms.

Description

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.

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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.

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Life Sciences
Provenance · 1 source records, 7 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE33353014 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[organism].NCBITaxon:10090source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title