ArticleToxicological sciences : an official journal of the Society of Toxicology2022
Checkpoint Inhibition Reduces the Threshold for Drug-Specific T-Cell Priming and Increases the Incidence of Sulfasalazine Hypersensitivity.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Immune checkpoint inhibitor-associated acute kidney injury in patients with cancer: a systematic review and meta-analysis of risk factors.Clinical and experimental nephrology · 2023Pooled it
- COLAR: open-label clinical study of IL-6 blockade with tocilizumab for the treatment of immune checkpoint inhibitor-induced colitis and arthritis.Journal for immunotherapy of cancer · 2022Trial
- Optimisation of in vitro assays for accurate risk assessment of T-cell responses to biologics with potential immune liabilities.Archives of toxicology · 2026Article
- Immune checkpoint blockade reshapes drug-associated toxicity: a pharmacovigilance atlas of drug-ICI interactions.medRxiv : the preprint server for health sciences · 2026Article
- The immunogenic potential of AZD1402 (Elarekibep) T-cell epitopes in healthy volunteers and drug-exposed clinical trial participants.Archives of toxicology · 2026Article
- Article
- Exploratory Clinical Study to Evaluate the Efficacy and Safety of Sulfasalazine for Immune Checkpoint Inhibitor (ICI)-Induced Colitis.JGH open : an open access journal of gastroenterology and hepatology · 2026Article
- Immunotherapy-induced hypersensitivity reaction to red tattoo ink.JAAD case reports · 2025Article
- Demographics, Overlap, and Latency of Severe Cutaneous Adverse Reactions in an FDA Database.medRxiv : the preprint server for health sciences · 2025Article
- Tolvaptan safety in autosomal-dominant polycystic kidney disease; a focus on idiosyncratic drug-induced liver injury liabilities.Toxicological sciences : an official journal of the Society of Toxicology · 2025Review
- Advancing drug safety in psychiatry: insights from pharmacogenomics of hypersensitivity reactions.Frontiers in pharmacology · 2025Review
- Immune checkpoint blockade lowers the threshold of naïve T-cell priming to drug-associated antigens in a dose-dependent fashion.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Immunological Drug-Drug Interactions Affect the Efficacy and Safety of Immune Checkpoint Inhibitor Therapies.Chemical research in toxicology · 2024Review
- Drug hypersensitivity reactions: review of the state of the science for prediction and diagnosis.Toxicological sciences : an official journal of the Society of Toxicology · 2024Review
- Protein Haptenation and Its Role in Allergy.Chemical research in toxicology · 2024Review
- Updates on the immunopathology and genomics of severe cutaneous adverse drug reactions.The Journal of allergy and clinical immunology · 2023Review
- Advances in understanding of the pathogenesis and therapeutic implications of drug reaction with eosinophilia and systemic symptoms: an updated review.Frontiers in medicine · 2023Review
- Practical Implementation of Genetics: New Concepts in Immunogenomics to Predict, Prevent, and Diagnose Drug Hypersensitivity.The journal of allergy and clinical immunology. In practice · 2022Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
Abstract
An emerging clinical issue associated with immune-oncology agents is the collateral effects on the tolerability of concomitant medications. One report of this phenomenon was the increased incidence of hypersensitivity reactions observed in patients receiving concurrent immune checkpoint inhibitors (ICIs) and sulfasalazine (SLZ). Thus, the aim of this study was to characterize the T cells involved in the pathogenesis of such reactions, and recapitulate the effects of inhibitory checkpoint blockade on de-novo priming responses to compounds within in vitro platforms. A regulatory competent human dendritic cell/T-cell coculture assay was used to model the effects of ICIs on de novo nitroso sulfamethoxazole- and sulfapyridine (SP) (the sulfonamide component of SLZ) hydroxylamine-specific priming responses. The role of T cells in the pathogenesis of the observed reactions was explored in 3 patients through phenotypic characterization of SP/sulfapyridine hydroxylamine (SPHA)-responsive T-cell clones (TCC), and assessment of cross-reactivity and pathways of T-cell activation. Augmentation of the frequency of responding drug-specific T cells and intensity of the T-cell response was observed with PD-1/PD-L1 blockade. Monoclonal populations of SP- and SPHA-responsive T cells were isolated from all 3 patients. A core secretory effector molecule profile (IFN-γ, IL-13, granzyme B, and perforin) was identified for SP and SPHA-responsive TCC, which proceeded through Pi and hapten mechanisms, respectively. Data presented herein provides evidence that drug-responsive T cells are effectors of hypersensitivity reactions observed in oncology patients administered ICIs and SLZ. Perturbation of drug-specific T-cell priming is a plausible explanation for clinical observations of how an increased incidence of these adverse events is occurring.
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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.