ArticleBMC cancer2023
Cholinergic signaling influences the expression of immune checkpoint inhibitors, PD-L1 and PD-L2, and tumor hallmarks in human colorectal cancer tissues and cell lines.
Article in BMC cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 17 citations in OpenAlex.
- Anisodus tanguticus in Cancer Research: A Review of Traditional Use, Phytochemistry, Extraction Methods, and Preclinical Antitumor Evidence.Medical science monitor : international medical journal of experimental and clinical research · 2026Review
- Neurotransmitters in cancer: how receptor signaling and posttranslational modifications modulate tumor progression and offer new therapeutic targets.Cell communication and signaling : CCS · 2026Review
- Neuron-tumor interplay in colorectal cancer: from mechanisms of onset and progression to targeted therapies.Cell communication and signaling : CCS · 2026Review
- Integrative In Silico Identification of TP53-Associated Drug Repurposing Candidates in Lung Adenocarcinoma.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Neuro-immune interactions in gastrointestinal oncology: Mechanisms, challenges, and therapeutic potential.Innovation (Cambridge (Mass.)) · 2026Review
- The neuro-vascular-immune triad: the interactive network in the tumor microenvironment.Cell communication and signaling : CCS · 2026Review
- Colitis-associated gut-vagus-brain signaling integrates tumorigenesis and neuroinflammation: comparative regulation by vagotomy and atropine.Journal of neuroinflammation · 2026Article
- Role of the neurotransmitter-receptor pathway in T-cell tumor immunology and cancer immunotherapy.Acta biochimica et biophysica Sinica · 2026Review
- Annurca Apple Extract and Colorectal Cancer Prevention: Preliminary In Silico Evaluation of Chlorogenic Acid.Diseases (Basel, Switzerland) · 2026Article
- Peripheral Nerve-Cancer Interactions in the Tumor Microenvironment: A Three-Dimensional Framework Integrating Mechanisms, Modulators, and Therapeutic Strategies.Research (Washington, D.C.) · 2026Review
- Advances in the study of the relationship between neurotransmitters and gastric cancer.World journal of gastroenterology · 2025Review
- Autonomic modulation of the immune response and implications for CNS malignancies.NPJ precision oncology · 2025Review
- Cholinergic Mechanisms in Gastrointestinal Neoplasia.International journal of molecular sciences · 2024Review
- Inhibition of IL-25/IL-17RA improves immune-related adverse events of checkpoint inhibitors and reveals antitumor activity.Journal for immunotherapy of cancer · 2024Article
- Novel Therapeutic Approaches for Colorectal Cancer Treatment.International journal of molecular sciences · 2024Article
- A Comprehensive Study on the Prognostic Value and Clinicopathological Significance of Different Immune Checkpoints in Patients With Colorectal Cancer: A Systematic Review and Meta-Analysis.Current therapeutic research, clinical and experimental · 2024Review
- Blocking Muscarinic Receptor 3 Attenuates Tumor Growth and Decreases Immunosuppressive and Cholinergic Markers in an Orthotopic Mouse Model of Colorectal Cancer.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCancer cells express immunosuppressive molecules, such as programmed death ligands (PD-L)1 and PD-L2, enabling evasion from the host's immune system. Cancer cells synthesize and secrete acetylcholine (ACh), acting as an autocrine or paracrine hormone to promote their proliferation, differentiation, and migration.
methodsWe correlated the expression of PD-L1, PD-L2, cholinergic muscarinic receptor 3 (M3R), alpha 7 nicotinic receptor (α7nAChR), and choline acetyltransferase (ChAT) in colorectal cancer (CRC) tissues with the stage of disease, gender, age, risk, and patient survival. The effects of a muscarinic receptor blocker, atropine, and a selective M3R blocker, 4-DAMP, on the expression of immunosuppressive and cholinergic markers were evaluated in human CRC (LIM-2405, HT-29) cells.
resultsIncreased expression of PD-L1, M3R, and ChAT at stages III-IV was associated with a high risk of CRC and poor survival outcomes independent of patients' gender and age. α7nAChR and PD-L2 were not changed at any CRC stages. Atropine and 4-DAMP suppressed the proliferation and migration of human CRC cells, induced apoptosis, and decreased PD-L1, PD-L2, and M3R expression in CRC cells via inhibition of EGFR and phosphorylation of ERK.
conclusionsThe expression of immunosuppressive and cholinergic markers may increase the risk of recurrence of CRC. These markers might be used in determining prognosis and treatment regimens for CRC patients. Blocking cholinergic signaling may be a potential therapeutic for CRC through anti-proliferation and anti-migration via inhibition of EGFR and phosphorylation of ERK. These effects allow the immune system to recognize and eliminate cancer cells.
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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 Socratic graph.