ArticleCancer immunology research2023
Combinatorial Immunotherapy with Agonistic CD40 Activates Dendritic Cells to Express IL12 and Overcomes PD-1 Resistance.
Article in Cancer immunology research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 15 citations in OpenAlex.
- CD40 agonism in renal cell carcinoma enhances immune checkpoint activity through myeloid cells.iScience · 2026Article
- CD40 Agonist Therapy in Melanoma: Translating Preclinical Promise Into Clinical Practice.Pigment cell & melanoma research · 2026Review
- Can tissue immune states shape the risk of hyperprogressive disease?Frontiers in immunology · 2026Review
- Targeting CTGF overcomes resistance to CSF1R inhibitors by preventing CAF activation in colorectal cancer.Cell reports. Medicine · 2025Article
- Arsenic Trioxide Enhances the Efficacy of PD-1 Inhibitors in Hepatocellular Carcinoma by Inducing Immunogenic Cell Death via the ROS/ERS Pathway.Immunity, inflammation and disease · 2025Article
- The genomic landscape of esophageal squamous cell carcinoma cell lines.Cancer cell international · 2025Article
- Scavenger Receptor CD36 in Tumor-Associated Macrophages Promotes Cancer Progression by Dampening Type-I IFN Signaling.Cancer research · 2025Article
- Mapping intratumoral myeloid-T cell interactomes at single-cell resolution reveals targets for overcoming checkpoint inhibitor resistance.bioRxiv : the preprint server for biology · 2024Article
- CD40 stimulation activates CD8+ T cells and controls HBV in CD4-depleted mice.JHEP reports : innovation in hepatology · 2024Article
- Single-Cell Analysis Reveals a Subset of High IL-12p40-Secreting Dendritic Cells within Mouse Bone Marrow-Derived Macrophages Differentiated with M-CSF.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Machine learning-based identification of an immunotherapy-related signature to enhance outcomes and immunotherapy responses in melanoma.Frontiers in immunology · 2024Article
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
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 CCL22+CCL5+ IL12-secreting DC subset as important early-stage effectors of triple therapy. CD4+ and CD8+ T cells are both critical effectors of treatment, and systems analysis of single-cell RNA sequencing data supported a role for DC-secreted IL12 in priming T-cell activation and recruitment. Finally, we showed that treatment with a novel IL12 mRNA therapeutic alone was sufficient to overcome PD-1 resistance and cause tumor regression. Overall, we conclude that combining myeloid-based innate immune activation and enhancement of adaptive immunity is a viable strategy to overcome anti-PD-1 resistance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.