ArticleCancer letters2021
CD137 agonist-based combination immunotherapy enhances activated, effector memory T cells and prolongs survival in pancreatic adenocarcinoma.
Article in Cancer letters, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 42 citations in OpenAlex.
- Current advances in immunotherapy for KRAS-Mutant pancreatic cancer.Clinical and experimental medicine · 2026Review
- Unveiling the Invisible: A Case of Canine Diffuse Microscopic Pancreatic Adenocarcinoma With Normal Imaging and Gross Appearance of the Pancreas Complicated by Sterile Peritonitis and Disseminated Intravascular Coagulation.Veterinary medicine and science · 2026Article
- Review
- The tumour microenvironment in pancreatic cancer - new clinical challenges, but more opportunities.Nature reviews. Clinical oncology · 2025Review
- Neoadjuvant Immunotherapy Promotes the Formation of Mature Tertiary Lymphoid Structures in a Remodeled Pancreatic Tumor Microenvironment.Cancer immunology research · 2025Article
- Cancer Vaccines and Beyond: The Transformative Role of Nanotechnology in Immunotherapy.Pharmaceutics · 2025Review
- Article
- Domestication and feedback: bidirectional hijacking in pancreatic ductal adenocarcinoma microenvironment.Frontiers in immunology · 2025Review
- Deciphering T-cell exhaustion in the tumor microenvironment: paving the way for innovative solid tumor therapies.Frontiers in immunology · 2025Review
- Extracellular vesicle surface display enhances the therapeutic efficacy and safety profile of cancer immunotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Current and future immunotherapeutic approaches in pancreatic cancer treatment.Journal of hematology & oncology · 2024Review
- Long-term activation of anti-tumor immunity in pancreatic cancer by a p53-expressing telomerase-specific oncolytic adenovirus.British journal of cancer · 2024Article
- Regulation of PD-L1 Expression by YY1 in Cancer: Therapeutic Efficacy of Targeting YY1.Cancers · 2024Review
- Clinical immunotherapy in pancreatic cancer.Cancer immunology, immunotherapy : CII · 2024Review
- Challenges and Opportunities in Targeting the Complex Pancreatic Tumor Microenvironment.JCO oncology advances · 2024Review
- Angiogenesis and Pancreatic Cancer: Novel Approaches to Overcome Treatment Resistance.Current cancer drug targets · 2024Review
- Therapeutic developments in pancreatic cancer.Nature reviews. Gastroenterology & hepatology · 2024Review
- Genetic alterations in the neuronal development genes are associated with changes of the tumor immune microenvironment in pancreatic cancer.Annals of pancreatic cancer · 2023Article
- CLDN18.2 BiTE Engages Effector and Regulatory T Cells for Antitumor Immune Response in Preclinical Models of Pancreatic Cancer.Gastroenterology · 2023Article
- Identification of MIR600HG/hsa-miR-342-3p/ANLN network as a potential prognosis biomarker associated with lmmune infiltrates in pancreatic cancer.Scientific reports · 2023Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Pancreatic ductal adenocarcinoma(PDAC) is resistant to the PD-1/PD-L1 blockade therapy. Previously, the combination of PD-1 blockade and vaccine therapy was shown to have a modest antitumor activity in murine models of PDAC. We used a murine syngeneic model of metastatic PDAC to identify, among multiple T cell modulators tested, which therapeutic agents in combination with the GVAX cancer vaccine and an anti-PD-1 antagonist antibody(αPD-1) are able to improve the survival. We found that an anti-CD137 agonist antibody(αCD137) most significantly improved survival in the mouse PDAC model. Moreover, αPD-1 and αCD137 together in combination with vaccine therapy more significantly increased the expression of costimulatory molecules CD137 and OX40 on CD4+PD-1+ and CD8+PD-1+ T cells comparing to αPD-1 or αCD137, respectively, suggesting that T cell activation within PDACs were enhanced by a synergy of αCD137 and αPD-1. On another hand, αCD137 treatment led to an increase in effector memory T cells independent of αPD-1. Although αCD137 does not increase the cytotoxic effector T cell function, the addition of αCD137 to GVAX+αPD-1 increased expression of IFNγ in EOMES + exhausted tumor-infiltrating T cells. Taken together, this preclinical study established the mechanism of targeting CD137 to enhance effector memory and activated T cells in PDAC. Immunohistochemistry analysis of resected human PDACs following the neo-adjuvant GVAX treatment showed increased levels of CD8
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