The Effect of Smoking on the Immune Microenvironment and Immunogenicity and Its Relationship With the Prognosis of Immune Checkpoint Inhibitors in Non-small Cell Lung Cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34660603", "kind": "science-record", "revision": 4, "content_hash": "sha256:1d1b7e0e25e03f90de5694dd59502350065a6ed241950ddc28c8cb63abd99ab9", "created_at": "2026-11-01T17:36:19Z", "updated_at": "2026-11-01T22:04:58Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "The Effect of Smoking on the Immune Microenvironment and Immunogenicity and Its Relationship With the Prognosis of Immune Checkpoint Inhibitors in Non-small Cell Lung Cancer.", "doi": "10.3389/fcell.2021.745859", "pmid": "34660603", "authors": ["Yueqin Sun", "Qi Yang", "Jie Shen", "Ting Wei", "Weitao Shen", "Nan Zhang", "Peng Luo", "Jian Zhang"], "journal": "Frontiers in cell and developmental biology", "year": 2021, "abstract": "Background: The emergence of immune checkpoint inhibitors (ICIs) has opened a new chapter for the treatment of non-small cell lung cancer (NSCLC), and the best beneficiaries of ICI treatment are still being explored. Smoking status has been repeatedly confirmed to affect the efficacy of ICIs in NSCLC patients, but the specific mechanism is still unclear. Methods: We performed analysis on the Memorial Sloan Kettering Cancer Center (MSKCC) clinical NSCLC cohort receiving ICI treatment, The Cancer Genome Atlas (TCGA) Pan-Lung Cancer cohort, and Gene Expression Omnibus (GEO) database GSE41271 lung cancer cohort that did not receive ICI treatment, including survival prognosis, gene mutation, copy number variation, immunogenicity, and immune microenvironment, and explored the impact of smoking status on the prognosis of NSCLC patients treated with ICIs and possible mechanism. In addition, 8 fresh NSCLC surgical tissue samples were collected for mass cytometry (CyTOF) experiments to further characterize the immune characteristics and verify the mechanism. Result: Through the analysis of the clinical data of the NSCLC cohort treated with ICIs in MSKCC, it was found that the smokers in NSCLC receiving ICI treatment had a longer progression-free survival (HR: 0.69, 95% CI: 0.49-0.97, p = 0.031) than those who never smoked. Further analysis of the TCGA and GEO validation cohorts found that the differences in prognosis between different groups may be related to the smoking group's higher immunogenicity, higher gene mutations, and stronger immune microenvironment. The results of the CyTOF experiment further found that the immune microenvironment of smoking group was characterized by higher expression of immune positive regulatory chemokine, and higher abundance of immune activated cells, including follicular helper CD4+ T cells, gamma delta CD4+ T cells, activated DC, and activated CD8+ T cells. In contrast, the immune microenvironment of non-smoking group was significantly enriched for immunosuppressive related cells, including regulatory T cells and M2 macrophages. Finally, we also found highly enriched CD45RAhighCD4+ T cells and CD45RAhighCD8+ T cells in the non-smoking group. Conclusion: Our research results suggest that among NSCLC patients receiving ICI treatment, the stronger immunogenicity and activated immune microenvironment of the smoking group make their prognosis better.", "claims": [{"id": "claim-method", "statement": "The Kaplan–Meier method and log-rank two-sided tests were used for survival analysis, with p < 0.05 accepted as statistically significant.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34660603", "locator": "sections[13] \"Statistical Analysis\" paragraph 2", "quote": "The Kaplan–Meier method and log-rank two-sided tests were used for survival analysis, with p < 0.05 accepted as statistically significant."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material. 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The CyTOF datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Through the analysis of the clinical data of the NSCLC cohort treated with ICIs in MSKCC, it was found that the smokers in NSCLC receiving ICI treatment had a longer progression-free survival (HR: 0.69, 95% CI: 0.49–0.97, p = 0.031) than those who never smoked.", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "Through the analysis of the clinical data of the NSCLC cohort treated with ICIs in MSKCC, it was found that the smokers in NSCLC receiving ICI treatment had a longer progression-free survival (HR: 0.69, 95% CI: 0.49–0.97, p = 0.031) than those who never smoked."}, "evidence": [{"asset": "source:pmid:34660603", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Through the analysis of the clinical data of the NSCLC cohort treated with ICIs in MSKCC, it was found that the smokers in NSCLC receiving ICI treatment had a longer progression-free survival (HR: 0.69, 95% CI: 0.49–0.97, p = 0.031) than those who never smoked."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Through the analysis of the clinical data of the NSCLC cohort treated with ICIs in MSKCC, it was found that the smokers in NSCLC receiving ICI treatment had a longer progression-free survival (HR: 0.69, 95% CI: 0.49–0.97, p = 0.031) than those who never smoked.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:34660603"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE41271"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE41271"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34660603", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fcell.2021.745859", "sha256": "sha256:79dd82072ad65b0cfd2406ee5e4e53c22faf994eb117ad3358b9dabcd6508f86", "bytes": 65224, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fcell.2021.745859", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8512705", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE41271", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE41271", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE41271", "version": null, "note": "The datasets presented in this study can be found in online repositories. 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