ArticleProceedings of the National Academy of Sciences of the United States of America2022
Aging-associated and CD4 T-cell-dependent ectopic CXCL13 activation predisposes to anti-PD-1 therapy-induced adverse events.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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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.
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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.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- Associations between tertiary lymphoid structure density and immune checkpoint inhibitor efficacy in solid tumors: systematic review and meta-analysis.Frontiers in immunology · 2024Pooled it
- B cells in cancer: functions, mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2026Review
- Advances and challenges in immunotherapy for intrahepatic cholangiocarcinoma based on the tumour immune microenvironment.Clinical and translational medicine · 2026Review
- Pharmacokinetic variability with pembrolizumab dosage switching and its impact on immune-related adverse events in patients with non-small cell lung cancer.Journal for immunotherapy of cancer · 2026Article
- Plasmatic CXCL13 as a biomarker of primary resistance to immunotherapy and impaired peripheral immunity in non-small cell lung cancer.Biomarker research · 2026Article
- Inflammation-Driven Lymphoid Structures: Organization, Function, and Clinical Impact Across Autoimmunity, Cancer, and Checkpoint Toxicity.Immunological reviews · 2026Review
- Plasma proteomics identify novel biomarkers and dynamic patterns of biological aging.Journal of advanced research · 2026Article
- Article
- From TLS architecture to functional immune niches: division of labor among CAFs, HEVs, and antigen-presenting cells in cancer immunotherapy.Frontiers in immunology · 2026Review
- Single-cell transcriptomic insights into the immune heterogeneity of immune checkpoint inhibitors related organ toxicities.Frontiers in immunology · 2026Review
- IL21 is predominantly produced by a CXCL13 associated CD4Frontiers in immunology · 2026Article
- Drug-induced adverse events in modern pharmacotherapy: mechanisms, clinical manifestations, and implications for risk assessment and management.Frontiers in pharmacology · 2026Review
- Immunotherapy-induced sialadenitis: sjögren's syndrome or a new sialadenitis.Frontiers in immunology · 2026Article
- Immunosenescence shapes the tumor immune microenvironment and limits PD-1/PD-L1 blockade efficacy in older patients with cancer.Frontiers in immunology · 2026Review
- Neutrophil extracellular traps-STC1 positive feedback loop promotes immune evasion and metastasis in bladder cancer.Journal for immunotherapy of cancer · 2025Article
- Ageing, immune fitness and cancer.Nature reviews. Cancer · 2025Review
- Metagenomic next-generation sequencing unraveled the characteristic of lung microbiota in patients with checkpoint inhibitor pneumonitis: results from a prospective cohort study.Journal for immunotherapy of cancer · 2025Observational
- Tertiary Lymphoid Structures Across Organs: Context, Composition, and Clinical Levers.Immunological reviews · 2025Review
- Reply to Letter to the Editor "Hepatic irAE, ICI continuation, and survival: need for robust evidence beyond initial observations".Hepatology international · 2025Article
- Neuromuscular complications associated with cancer immunotherapy.Journal of the National Cancer Center · 2025Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clinical success of immune-checkpoint blockade (ICB) cancer immunotherapy is compromised by increased risk of immune-related adverse events (irAEs). However, mechanistic action(s) of immune responses underlying development of irAE remain not fully explored. Here, we found that in tumor-bearing aged, but not young, mice, antiprogrammed death receptor (PD)-1 therapy elicited irAE-like multiorgan dysfunctions with ectopic accumulation of T and B cells in damaged organs. In this preclinical model, the organ toxicities were mediated by immunoglobulin G (IgG) deposition because administration of IG from ICB-treated aged mice induced the pathogenicity specifically in naïve aged hosts. Mechanistically, CD4 T-cell-derived interleukin (IL)-21 upregulated B-cell-homing chemokine, CXCL13, preferentially in irAE organs from aged mice treated with anti-PD-1 therapy. The ICB-induced pathogenicity was alleviated by B-cell depletion or by blockade of IL-21 or CXCL13 activity. These results suggest that age-associated immune regulatory milieu contributes to the formation of tertiary lymphoid structure-like lymphocytic aggregates in irAE organs and irAE-related toxicity employing IL-21-CXCL13-auto-antibody axis. Supporting this, a systemic increase in CXCL13 and
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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.