ArticleCancer immunology research2015
Induction of T-cell Immunity Overcomes Complete Resistance to PD-1 and CTLA-4 Blockade and Improves Survival in Pancreatic Carcinoma.
Article in Cancer immunology research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 300 papers, 2 of them syntheses that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
300 citing papers in PubMed, 2 syntheses or guidelines pooled it, 460 citations in OpenAlex.
- Global assessment of hepatic safety in novel immunotherapies: a systematic review and meta-analysis.Frontiers in immunology · 2025Pooled it
- Immune checkpoint inhibition for pancreatic ductal adenocarcinoma: limitations and prospects: a systematic review.Cell communication and signaling : CCS · 2021Pooled it
- Sotigalimab and/or nivolumab with chemotherapy in first-line metastatic pancreatic cancer: clinical and immunologic analyses from the randomized phase 2 PRINCE trial.Nature medicine · 2022Trial
- The 15-year bibliometric landscape of glioblastoma vaccines: Emergence of combinatorial immunotherapy.Human vaccines & immunotherapeutics · 2026Review
- Oncogenic Kras targeting with MRTX1133 or Daraxonrasib specifically synergize with anti-CTLA4 to promote anti-tumor immunity in pancreatic cancer.Nature communications · 2026Article
- CD40 Agonist Therapy in Melanoma: Translating Preclinical Promise Into Clinical Practice.Pigment cell & melanoma research · 2026Review
- Hypoxia-inducible factors: Regulatory functions and status as a therapeutic target in gastric cancer (Review).Oncology letters · 2026Review
- CD40 Agonism in Pancreatic Ductal Adenocarcinoma: Expression, Biology, and Therapeutic Targeting.Cancers · 2026Review
- Article
- KRAS Inhibitors in Pancreas Cancer: Facts and Hopes about the Immunotherapy We Have All Been Waiting for.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Review
- Article
- Phase I(b) study evaluating the safety and efficacy of intratumoral agonistic anti-CD40 (selicrelumab) in combination with anti-PD-L1 (atezolizumab) in patients with refractory or relapsed B-cell lymphoma (ITSELF trial).Immuno-oncology technology · 2026Article
- Microenvironmental regulation of solid tumour resistance to CAR T cell therapy.Nature reviews. Immunology · 2026Review
- Clinical and translational results from a phase 1 trial of gemcitabine/nab-paclitaxel with nivolumab/ipilimumab or hydroxychloroquine/ipilimumab in untreated metastatic pancreatic adenocarcinoma.Journal for immunotherapy of cancer · 2026Article
- Tumor Microenvironment: Insights from Multiparametric MRI in Pancreatic Ductal Adenocarcinoma.Cancers · 2026Article
- Agonistic CD40 elicits CD8+ T-cell-dependent primary responses and CD4+ T-cell-dependent long-term immunity in breast cancer.NPJ breast cancer · 2026Article
- Aryl Hydrocarbon Receptor Ligands Drive Pancreatic Cancer Initiation and Progression through Protumorigenic T-cell Polarization.Cancer discovery · 2026Article
- CD4+ T Cells Mediate MHC-Deficient Tumor Rejection and Endothelial Cell Reprogramming.Cancer immunology research · 2026Article
- Targeting VISTA as a novel immunotherapy for skin cancer.Frontiers in immunology · 2026Review
- A Combinatorial Effect of Immune Checkpoint Inhibitors and CD40 Agonistic Antibody in Murine Pancreatic Cancer Model.Cancer science · 2026Article
240 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Disabling the function of immune checkpoint molecules can unlock T-cell immunity against cancer, yet despite remarkable clinical success with monoclonal antibodies (mAb) that block PD-1 or CTLA-4, resistance remains common and essentially unexplained. To date, pancreatic carcinoma is fully refractory to these antibodies. Here, using a genetically engineered mouse model of pancreatic ductal adenocarcinoma in which spontaneous immunity is minimal, we found that PD-L1 is prominent in the tumor microenvironment, a phenotype confirmed in patients; however, tumor PD-L1 was found to be independent of IFNγ in this model. Tumor T cells expressed PD-1 as prominently as T cells from chronically infected mice, but treatment with αPD-1 mAbs, with or without αCTLA-4 mAbs, failed in well-established tumors, recapitulating clinical results. Agonist αCD40 mAbs with chemotherapy induced T-cell immunity and reversed the complete resistance of pancreatic tumors to αPD-1 and αCTLA-4. The combination of αCD40/chemotherapy plus αPD-1 and/or αCTLA-4 induced regression of subcutaneous tumors, improved overall survival, and conferred curative protection from multiple tumor rechallenges, consistent with immune memory not otherwise achievable. Combinatorial treatment nearly doubled survival of mice with spontaneous pancreatic cancers, although no cures were observed. Our findings suggest that in pancreatic carcinoma, a nonimmunogenic tumor, baseline refractoriness to checkpoint inhibitors can be rescued by the priming of a T-cell response with αCD40/chemotherapy.
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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.