ArticleCancer cell2022
The allergy mediator histamine confers resistance to immunotherapy in cancer patients via activation of the macrophage histamine receptor H1.
Article in Cancer cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 156 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
156 citing papers in PubMed, 3 syntheses or guidelines pooled it, 293 citations in OpenAlex.
- Correlation between allergy and cancer: a systematic review and meta-analysis.Scientific reports · 2025Pooled it
- PD-1/PD-L1 immune checkpoint blockade in breast cancer: research insights and sensitization strategies.Molecular cancer · 2024Pooled it
- Exploring the interactions of antihistamine with retinoic acid receptor beta (RARB) by molecular dynamics simulations and genome-wide meta-analysis.Journal of molecular graphics & modelling · 2023Pooled it
- Mobilizing antigen-presenting mast cells in anti-PD-1-refractory triple-negative breast cancer: a phase 2 trial.Nature medicine · 2025Trial
- Effect of Clemastine Fumarate on Perioperative Hemodynamic Instability Mediated by Anaphylaxis During Cardiopulmonary Bypass Surgery.Medical science monitor : international medical journal of experimental and clinical research · 2022Trial
- Targeting histamine signaling: repurposing antihistamines for cancer chemotherapy and immunotherapy.Archives of pharmacal research · 2026Review
- METLUNG: plasma metabolomic profiling identifies metabolomic signatures associated with immunotherapy outcomes in non-small cell lung cancer.Journal for immunotherapy of cancer · 2026Observational
- VISTA+ Neutrophils Contribute to Platinum Resistance by Suppressing CD8+ T Cells in High-Grade Serous Ovarian Cancer.Cancer immunology research · 2026Article
- Targeting the nervous system: Mechanistic insights into neuro-tumor communication and therapeutic opportunities.Acta pharmaceutica Sinica. B · 2026Review
- Neural regulation in lung cancer: from mechanisms to new therapeutic perspectives.Clinical and experimental medicine · 2026Review
- Endogenous metabolite signaling orchestrates tumor immune evasion.Cell insight · 2026Review
- A HRH1-YAP1 feedback loop drives pancreatic cancer progression and predicts therapeutic response.Oncology letters · 2026Article
- Metabolic determinants of cancer immunotherapy outcomes identified by plasma profiling.Nature medicine · 2026Article
- Gut microbiota and its metabolites: Key factors of drug resistance in the treatment of advanced prostate cancer (Review).Molecular medicine reports · 2026Review
- Histidine to glutamine substitutants, a regulated process that impacts cell survival and suggests histidine shortage in cancer.Cell death discovery · 2026Article
- Macrophage ALDH2 drives immunotherapy resistance by silencing CXCL9 through metabolic-epigenetic crosstalk.Nature communications · 2026Article
- SLC22A3 deficiency leads to cognitive impairment through the cardio-neuroinflammatory axis mediated HA/H1R/NLRP3 pathway in heart failure mice.Redox biology · 2026Article
- Cetirizine suppresses cancer-associated fibroblast-mediated fibrotic remodeling and epithelial-mesenchymal transition via histamine HBreast cancer research : BCR · 2026Article
- Loss of Mast cells and histaminergic signaling link diet to platelet-mediated NETosis and mammary cancer recurrence.bioRxiv : the preprint server for biology · 2026Article
- Drug allergy history predicts early progression-free survival benefit from PD-(L)1 inhibitors in advanced non-small cell lung cancer: a retrospective cohort study.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
96 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
- Commented on by
Authors and funding
20 authors at 6 institutions in 3 countries.
Funding
Abstract
Reinvigoration of antitumor immunity remains an unmet challenge. Our retrospective analyses revealed that cancer patients who took antihistamines during immunotherapy treatment had significantly improved survival. We uncovered that histamine and histamine receptor H1 (HRH1) are frequently increased in the tumor microenvironment and induce T cell dysfunction. Mechanistically, HRH1-activated macrophages polarize toward an M2-like immunosuppressive phenotype with increased expression of the immune checkpoint VISTA, rendering T cells dysfunctional. HRH1 knockout or antihistamine treatment reverted macrophage immunosuppression, revitalized T cell cytotoxic function, and restored immunotherapy response. Allergy, via the histamine-HRH1 axis, facilitated tumor growth and induced immunotherapy resistance in mice and humans. Importantly, cancer patients with low plasma histamine levels had a more than tripled objective response rate to anti-PD-1 treatment compared with patients with high plasma histamine. Altogether, pre-existing allergy or high histamine levels in cancer patients can dampen immunotherapy responses and warrant prospectively exploring antihistamines as adjuvant agents for combinatorial immunotherapy.
Indexed as
Identifiers
What OpenQuestion holds
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.