CELL INTELLIGENCE · 肿瘤细胞治疗研究

CELLIN 肿瘤细胞治疗研究

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亚型特异性 NK 细胞-TAM 相互作用驱动头颈部鳞状细胞癌的新型预后特征

英文原题：Subtype-specific NK cell-TAM interactions drive a novel prognostic signature in HNSCC.

查看英文原题

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

PubMed 2025/10/17（内容时间） Front Immunol Q1 · IF 7（JCR 2025）

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技术：NK 细胞头颈部鳞癌地区：中国
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研究概要

本研究揭示了 HNSCC 中亚型特异性的 NK-TAM 相互作用，并将 CINT 作为一种稳健的预后和免疫治疗反应模型，为免疫微环境靶向治疗提供了新策略。

研究思路结论见上方概要

背景

头颈鳞状细胞癌（HNSCC）的免疫微环境高度复杂，自然杀伤（NK）细胞与肿瘤相关巨噬细胞（TAM）之间相互作用的机制尚不清楚。本研究通过多组学分析探讨NK-TAM crosstalk的细胞异质性、相互作用模式及预后意义。

方法

共分析58份HNSCC组织样本。通过免疫组化（CD16、CD64、CD163）、单细胞RNA测序（GSE139324）及公共数据库（TCGA-HNSC、GSE65858）鉴定NK和TAM亚群。使用CellChat推断配体-受体相互作用，通过CSOmap算法评估空间邻近性并经免疫荧光验证。采用LASSO Cox回归构建预后模型，并在免疫治疗队列（PRJEB23709、phs000452.v2.p1）中验证。

结果

高 CD16/CD64 表达与良好预后相关，而 CD163 提示不良结局（P < 0.05）。NK 细胞分为 IL32+NK（抗病毒、T 细胞活化）、NFKBIA+NK（核糖体相关）和 STMN1+NK（DNA 修复相关）亚群。TAM 包括 APOE+TAM（M2 样）、IL1B+/CXCL10+TAM（M1 样）和 HSP+TAM（应激反应性）。IL32+NK 通过 SPP1、MIF 和 ITGB2 通路与 APOE+TAM 和 CXCL10+TAM 相互作用最强。空间定位和免疫荧光证实了 IL32 与 CXCL10 的邻近性和正相关（R = 0.641，P < 0.001），与 APOE 负相关（R=-0.686，P < 0.001）。一个 23 基因 NK-TAM 相互作用相关特征（CINT）在训练队列和验证队列中有效分层患者风险（P < 0.05），并预测免疫治疗患者的生存获益。

展开英文摘要原文
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.

METHODS

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).

RESULTS

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.

CONCLUSION

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.

论文信息

作者
Zhao Z、Han X、Hu Y、Li Y、He Y、Wang Y、Yao Y、Li H
单位
State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi'an,&#xa0;China.China
期刊
Frontiers in immunology2025
原文标识
PubMed 41181127　·　DOI 10.3389/fimmu.2025.1676878

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