ArticleNature communications2022
Targeting vasoactive intestinal peptide-mediated signaling enhances response to immune checkpoint therapy in pancreatic ductal adenocarcinoma.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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Who cites it
29 citing papers in PubMed, 33 citations in OpenAlex.
- Neuroimmune crosstalk in cancer: emerging immunotherapeutic opportunities.Journal for immunotherapy of cancer · 2026Review
- Mechanisms of neuropeptide-mediated immune sensing in the modulation of antitumor immunity.Journal for immunotherapy of cancer · 2026Review
- Neural-tumor interactions: bidirectional regulatory mechanisms and nervous system-targeted tumor therapeutic strategies.Biomarker research · 2026Review
- Targeting the nervous system: Mechanistic insights into neuro-tumor communication and therapeutic opportunities.Acta pharmaceutica Sinica. B · 2026Review
- Neural regulation of tumor immunity: emerging opportunities to enhance cancer immunotherapy.Experimental & molecular medicine · 2026Review
- Neuropeptide Y as a Neuro-Immune Checkpoint in Cancer.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026Review
- Effects of different dietary methionine and cysteine ratios on growth performance and intestinal development of broilers from brain-gut peptide secretion perspective.Animal bioscience · 2026Article
- Neuro-immune interactions in gastrointestinal oncology: Mechanisms, challenges, and therapeutic potential.Innovation (Cambridge (Mass.)) · 2026Review
- Review
- Identification and characterization of vasoactive intestinal peptide receptor antagonists with high-affinity and potent anti-leukemia activity.The Journal of biological chemistry · 2026Article
- Regulators of CD8Nature reviews. Immunology · 2026Review
- CGRP at the Neuroimmune Interface: Regulator of Host Defense, Tumor Immunity, and Tissue Homeostasis.Research (Washington, D.C.) · 2026Review
- Peripheral Nerve-Cancer Interactions in the Tumor Microenvironment: A Three-Dimensional Framework Integrating Mechanisms, Modulators, and Therapeutic Strategies.Research (Washington, D.C.) · 2026Review
- Targeted drug delivery systems for pancreatic cancer therapy: advances, challenges, and future perspectives.Frontiers in immunology · 2026Review
- T cell-macrophage crosstalk in GVHD and cancer immunotherapy.Cell investigation · 2025Article
- Turning cold tumors into hot tumors to ignite immunotherapy.Molecular cancer · 2025Review
- Neuro-immune cross-talk in cancer.Nature reviews. Cancer · 2025Review
- Pancreatic cancer cell-intrinsic transglutaminase-2 promotes T cell suppression through microtubule-dependent secretion of immunosuppressive cytokines.Journal for immunotherapy of cancer · 2025Article
- Nerves, nodes, and neoplasia.Frontiers in immunology · 2025Review
- Muc16CD is a novel CAR T cell target antigen for the treatment of pancreatic cancer.Molecular therapy. Oncology · 2024Article
Corrections and comments
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Authors and funding
21 authors at 3 institutions in 1 country.
Funding
Abstract
A paucity of effector T cells within tumors renders pancreatic ductal adenocarcinoma (PDAC) resistant to immune checkpoint therapies. While several under-development approaches target immune-suppressive cells in the tumor microenvironment, there is less focus on improving T cell function. Here we show that inhibiting vasoactive intestinal peptide receptor (VIP-R) signaling enhances anti-tumor immunity in murine PDAC models. In silico data mining and immunohistochemistry analysis of primary tumors indicate overexpression of the neuropeptide vasoactive intestinal peptide (VIP) in human PDAC tumors. Elevated VIP levels are also present in PDAC patient plasma and supernatants of cultured PDAC cells. Furthermore, T cells up-regulate VIP receptors after activation, identifying the VIP signaling pathway as a potential target to enhance T cell function. In mouse PDAC models, VIP-R antagonist peptides synergize with anti-PD-1 antibody treatment in improving T cell recruitment into the tumors, activation of tumor-antigen-specific T cells, and inhibition of T cell exhaustion. In contrast to the limited single-agent activity of anti-PD1 antibodies or VIP-R antagonist peptides, combining both therapies eliminate tumors in up to 40% of animals. Furthermore, tumor-free mice resist tumor re-challenge, indicating anti-cancer immunological memory generation. VIP-R signaling thus represents a tumor-protective immune-modulatory pathway that is targetable in PDAC.
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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.