{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Krykbaeva I"],"funding":["National Cancer Institute","NCI NIH HHS"],"pagination":["1332-1350"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12645833"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11(10)"],"pubmed_abstract":["Checkpoint inhibitors have revolutionized cancer treatment, but resistance remains a significant clinical challenge. Myeloid cells within the tumor microenvironment can modulate checkpoint resistance by either supporting or suppressing adaptive immune responses. Using an anti-PD-1-resistant mouse melanoma model, we show that targeting the myeloid compartment via CD40 activation and CSF1R blockade in combination with anti-PD-1 results in complete tumor regression in a majority of mice. This triple therapy combination was primarily CD40 agonist-driven in the first 24 hours after therapy and showed a similar systemic cytokine profile in human patients as was seen in mice. Functional single-cell cytokine secretion profiling of dendritic cells (DC) using a novel microwell assay identified a CCL"],"journal":["Cancer immunology research"],"pubmed_title":["Combinatorial Immunotherapy with Agonistic CD40 Activates Dendritic Cells to Express IL12 and Overcomes PD-1 Resistance."],"pmcid":["PMC12645833"],"funding_grant_id":["F30 CA228444","U01CA238728","U01 CA238728","F30CA228444"],"pubmed_authors":["Weiss SA","Park K","Olino K","Bridges K","Kluger HM","McGeary MK","Miller-Jensen K","Alexander AF","Kaech SM","Pizzurro GA","Eyles J","Turner N","Krykbaeva I","Damsky W","Bosenberg M","Luheshi N","Muthusamy V"],"additional_accession":[]},"is_claimable":false,"name":"Combinatorial Immunotherapy with Agonistic CD40 Activates Dendritic Cells to Express IL12 and Overcomes PD-1 Resistance.","description":"Checkpoint inhibitors have revolutionized cancer treatment, but resistance remains a significant clinical challenge. Myeloid cells within the tumor microenvironment can modulate checkpoint resistance by either supporting or suppressing adaptive immune responses. Using an anti-PD-1-resistant mouse melanoma model, we show that targeting the myeloid compartment via CD40 activation and CSF1R blockade in combination with anti-PD-1 results in complete tumor regression in a majority of mice. This triple therapy combination was primarily CD40 agonist-driven in the first 24 hours after therapy and showed a similar systemic cytokine profile in human patients as was seen in mice. Functional single-cell cytokine secretion profiling of dendritic cells (DC) using a novel microwell assay identified a CCL","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Oct","modification":"2026-06-05T19:11:42.132Z","creation":"2026-05-20T03:14:33.872Z"},"accession":"S-EPMC12645833","cross_references":{"pubmed":["37478171"],"doi":["10.1158/2326-6066.CIR-22-0699","10.1158/2326-6066.cir-22-0699"]}}