A novel immune signature predicts immunotherapy responsiveness and reveals the landscape of the tumor immune microenvironment in head and neck squamous cell carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36437964", "kind": "science-record", "revision": 3, "content_hash": "sha256:a97a3a2edf382b8bea31c607a05358246af35bac3b2034f7d1178e5d7273a832", "created_at": "2026-11-01T19:00:54Z", "updated_at": "2026-11-01T22:08:10Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A novel immune signature predicts immunotherapy responsiveness and reveals the landscape of the tumor immune microenvironment in head and neck squamous cell carcinoma.", "doi": "10.3389/fgene.2022.1051051", "pmid": "36437964", "authors": ["Qiwei Wang", "Yinan Zhao", "Fang Wang", "Guolin Tan"], "journal": "Frontiers in genetics", "year": 2022, "abstract": "Background: Immune-checkpoint blockade (ICB) has been routinely implemented to treat head and neck squamous cell carcinoma (HNSCC) patients. However, only a few patients benefit from immune checkpoint inhibitor (ICI) therapies. Methods: In this study, we used a combined cohort (including the GSE41613, GSE65858, TCGA, and CELL cohorts) to identify hub genes significantly associated with ICB and activated CD8+ T-cell gene signatures. We performed single-sample gene set enrichment analysis (ssGSEA) to quantify the expression of hub genes; we then constructed a novel immune signature named \"the IMS\" that can predict immunotherapy responsiveness, prognosis, immune infiltration, and clinical characteristics. Data from the GSE102349 external cohort and the pembrolizumab cohort obtained from a clinical trial were used to validate the efficiency of the IMS. In addition, we revealed potential mechanisms of the antitumor response by analyzing the HNSCC single-cell database. Finally, we used the LASSO algorithm to build an IMS-related risk model. Results: The high IMS group was associated with significant immune activation, better prognosis, and increased immunotherapy responsiveness; thus, the IMS potentially represents a candidate biomarker for ICB. Moreover, a tumor microenvironment with a higher IMS underwent remarkable metabolic reprogramming characterized by enrichment in the glycolysis/gluconeogenesis, oxidative phosphorylation, and citrate cycle (TCA cycle) pathways. We also revealed key information on cellular crosstalk between the IMS and other immune lineages, which may mechanistically explain immune escape. In addition, we constructed and validated a risk prediction model (CD2, TBC1D10C, and CD3E) that could stratify HNSCC patients based on survival and response to ICB treatment. Conclusion: IMS is a signature closely correlated with the tumor immune microenvironment. The findings of this study contribute to the understanding of the immune landscape in HNSCC patients. IMS may aid in the clinical management of HNSCC patients through the identification of effective immunotherapies for specific patients.", "claims": [{"id": "claim-method", "statement": "We used LASSO regression to filter optimal prognostic gene combinations to classify our combined cohort.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36437964", "locator": "sections[9] \"Construction and verification of the prognostic model\" paragraph 2", "quote": "We used LASSO regression to filter optimal prognostic gene combinations to classify our combined cohort."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All datasets used in this study are available in a public database. The codes supporting the conclusions of this article can be obtained by reasonable request to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36437964", "locator": "sections[11] \"Data and code availability statements\" paragraph 2", "quote": "All datasets used in this study are available in a public database. The codes supporting the conclusions of this article can be obtained by reasonable request to the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The high IMS group was associated with significant immune activation, better prognosis, and increased immunotherapy responsiveness; thus, the IMS potentially represents a candidate biomarker for ICB.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36437964", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The high IMS group was associated with significant immune activation, better prognosis, and increased immunotherapy responsiveness; thus, the IMS potentially represents a candidate biomarker for ICB."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The high IMS group was associated with significant immune activation, better prognosis, and increased immunotherapy responsiveness; thus, the IMS potentially represents a candidate biomarker for ICB.", "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:36437964"], "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. 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