Subtype-specific NK cell-TAM interactions drive a novel prognostic signature in HNSCC.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41181127", "kind": "science-record", "revision": 4, "content_hash": "sha256:05047089faa2c7133c7b4508dc277d2d328db2419bd875ed949fac92a7863cff", "created_at": "2026-11-01T20:31:13Z", "updated_at": "2026-11-01T22:57:23Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Subtype-specific NK cell-TAM interactions drive a novel prognostic signature in HNSCC.", "doi": "10.3389/fimmu.2025.1676878", "pmid": "41181127", "authors": ["Zhenyan Zhao", "Xuejiao Han", "Yating Hu", "Yun Li", "Yaodong He", "Yan Wang", "Yanbing Yao", "Huan Li", "Jianhua Wei"], "journal": "Frontiers in immunology", "year": 2025, "abstract": "Background: The immune microenvironment of head and neck squamous cell carcinoma (HNSCC) is highly complex, and the mechanisms underlying interactions between natural killer (NK) cells and tumor-associated macrophages (TAMs) remain unclear. This study investigates the cellular heterogeneity, interaction patterns, and prognostic significance of NK-TAM crosstalk through multi-omics analyses.\nMethods: A total of 58 HNSCC tissue samples were analyzed. NK and TAM subsets were identified using immunohistochemistry (CD16, CD64, CD163), single-cell RNA sequencing (GSE139324), and public databases (TCGA-HNSC, GSE65858). CellChat was used to infer ligand-receptor interactions, while spatial proximity was assessed via the CSOmap algorithm and validated by immunofluorescence. A prognostic model was constructed using LASSO Cox regression and validated in an immunotherapy cohort (PRJEB23709, phs000452.v2.p1).\nResults: High CD16/CD64 expression correlated with favorable prognosis, while CD163 indicated poor outcomes (P < 0.05). NK cells were divided into IL32+NK (antiviral, T cell-activating), NFKBIA+NK (ribosome-related), and STMN1+NK (DNA repair-related) subsets. TAMs included APOE+TAM (M2-like), IL1B+/CXCL10+TAM (M1-like), and HSP+TAM (stress-responsive). IL32+NK interacted most strongly with APOE+TAM and CXCL10+TAM via SPP1, MIF, and ITGB2 pathways. Spatial mapping and immunofluorescence confirmed proximity and a positive correlation between IL32 and CXCL10 (R = 0.641, P < 0.001), and a negative correlation with APOE (R=-0.686, P < 0.001). A 23-gene NK-TAM interaction-related signature (CINT) effectively stratified patient risk in both training and validation cohorts (P < 0.05) and predicted survival benefit in immunotherapy-treated patients.\nConclusion: This study uncovers subtype-specific NK-TAM interactions in HNSCC and introduces CINT as a robust prognostic and immunotherapy response model, offering a new strategy for immune microenvironment-targeted therapy.", "claims": [{"id": "claim-method", "statement": "LASSO regression analysis (using the R package glmnet) was employed to further select key prognostic factors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41181127", "locator": "sections[12] \"Construction and validation of prognostic biomarkers based on cellular interaction mechanisms\" paragraph 4", "quote": "LASSO regression analysis (using the R package glmnet) was employed to further select key prognostic factors."}], "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 .", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41181127", "locator": "sections[26] \"Data availability statement\" paragraph 2", "quote": "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 ."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A 23-gene NK-TAM interaction–related signature (CINT) effectively stratified patient risk in both training and validation cohorts (P < 0.05) and predicted survival benefit in immunotherapy-treated patients.", "kind": "quantitative", "target": {"value": 0.05, "unit": "p-value", "tolerance": null, "source": "A 23-gene NK-TAM interaction–related signature (CINT) effectively stratified patient risk in both training and validation cohorts (P < 0.05) and predicted survival benefit in immunotherapy-treated patients."}, "evidence": [{"asset": "source:pmid:41181127", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "A 23-gene NK-TAM interaction–related signature (CINT) effectively stratified patient risk in both training and validation cohorts (P < 0.05) and predicted survival benefit in immunotherapy-treated patients."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A 23-gene NK-TAM interaction–related signature (CINT) effectively stratified patient risk in both training and validation cohorts (P < 0.05) and predicted survival benefit in immunotherapy-treated patients.", "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:41181127"], "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:GSE139324"], "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:GSE139324"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:41181127", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fimmu.2025.1676878", "sha256": "sha256:9ad8298e69714760b2262b9b0ca2d7b5cf6de175ac628deefbab753dbaaeccab", "bytes": 53489, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fimmu.2025.1676878", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12575298", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE139324", "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=GSE139324", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE139324", "version": null, "note": "The datasets presented in this study can be found in online repositories. 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