ArticleJournal for immunotherapy of cancer2023
Tobacco exposure primes the secretion of CCL21 positively associated with tertiary lymphoid structure and response to immunotherapy.
Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- B cells in cancer: functions, mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2026Review
- Neural regulation in lung cancer: from mechanisms to new therapeutic perspectives.Clinical and experimental medicine · 2026Review
- scComm: a contrastive learning framework for deciphering cell-cell communications at single-cell resolution.Genome biology · 2026Article
- From TLS architecture to functional immune niches: division of labor among CAFs, HEVs, and antigen-presenting cells in cancer immunotherapy.Frontiers in immunology · 2026Review
- The Sunrise of Tertiary Lymphoid Structures in Cancer.Immunological reviews · 2025Review
- Impact of Tertiary Lymphoid Structure on Prognosis and Tumor Microenvironment in Undifferentiated Pleomorphic Sarcoma.Cancer science · 2025Article
- ACAT1 regulates tertiary lymphoid structures and correlates with immunotherapy response in non-small cell lung cancer.The Journal of clinical investigation · 2025Article
- From heterogeneity to prognosis: understanding the complexity of tertiary lymphoid structures in tumors.Molecular biology reports · 2025Review
- Article
- Tertiary lymphoid structures in esophageal cancer: a novel target for immunotherapy.Frontiers in immunology · 2025Review
- A causal association between chemokines and the risk of lung cancer: a univariate and multivariate mendelian randomization study.Journal of cardiothoracic surgery · 2024Article
- CCL21 Induces Plasmacytoid Dendritic Cell Migration and Activation in a Mouse Model of Glioblastoma.Cancers · 2024Article
- Lifetime Exposure to Cigarette Smoke, B-Cell Tumor Immune Infiltration, and Immunoglobulin Abundance in Ovarian Tumors.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2024Article
- Review
- Tertiary lymphoid structures in cancer: maturation and induction.Frontiers in immunology · 2024Review
- Heterogeneity of tertiary lymphoid structures in cancer.Frontiers in immunology · 2023Review
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIt has been reported that smoking history as a predictor of immunotherapy efficacy in patients with advanced lung cancer, however, the underlying mechanisms of this phenomenon remain largely unknown.
methodsThe patients with lung adenocarcinoma's (LUAD) cohort and the orthotopical transplanted mouse model were used to explore the correlation between smoking status and tertiary lymphoid structure (TLS) and chemokine CCL21, respectively. Cell adhesion and co-immunoprecipitation assays were performed to explore the interaction between CD4+T cells and CD20+B cells under tobacco exposure. Chromatin immunoprecipitation-PCR was used to dissect the mechanism of upregulated CCL21 secretion in tobacco treatment. Serum CCL21 level was recorded in patients with LUAD treated with immunotherapy.
resultsHere we observed that individuals with a smoking history exhibit an increased quantity and maturation level of TLS compared with non-smokers, along with higher levels of CCL21 secretion. Tobacco exposure promoted CCL21 expression in an epithelial cell-intrinsic manner, of which BaP, the main component of tobacco, facilitated the nuclear retention of the aryl hydrocarbon receptor that occupied the promoter of CCL21. Additionally, the activated CCL21/CCR7 axis increased the CD11a expression of CD4+T cells, boosting the interaction with CD20+B cells dependent on ICAM1, which potentially induced the TLSs formation. Patients with elevated serum levels of CCL21 benefited more from immunotherapy.
conclusionsPatients with a smoking history exhibited higher levels of TLS via the CCL21-dependent mechanism, serum CCL21 was identified as a reliable biomarker for predicting the efficacy of immunotherapy.
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