CXCL10与皮肤黑色素瘤预后良好相关并指示提示干扰素驱动的免疫活性表型

CXCL10 Expression Predicts Favorable Prognosis and Defines an Interferon-Driven Immune-Active Phenotype in Skin Cutaneous Melanoma

摘要: CXCL10是一种由干扰素γ诱导产生的趋化因子，可招募CXCR3⁺的T细胞和NK细胞，在抗肿瘤免疫调控中发挥关键作用，但其在黑色素瘤中的预后意义及细胞来源尚未明确。本研究整合TCGA的bulkRNA-seq数据与TISCH数据库中的单细胞转录组数据，系统分析了CXCL10在皮肤黑色素瘤(SKCM)中的表达特征、预后价值、免疫相关性及生物学背景。结果显示，CXCL10高表达显著预测更长的总体生存期，并标记出一种干扰素驱动的免疫活性肿瘤表型，其特征为细胞毒性相关分子及抗原呈递相关通路的上调；而低表达肿瘤则富集黑色素细胞谱系与色素生成相关基因程序。相关性分析表明，CXCL10与CD8A、GZMB、PRF1、HLA分子及PDCD1、CTLA4等免疫检查点基因强相关，反映出协调一致的适应性免疫激活特征。单细胞分析进一步显示，在三个独立队列中，CXCL10主要由肿瘤相关巨噬细胞和树突状细胞产生，而在肿瘤细胞及淋巴细胞中表达极低。综上所述，CXCL10是皮肤黑色素瘤中干扰素介导免疫活化与良好预后的可靠标志物，其髓系来源的表达特征强调了先天免疫在塑造免疫炎症型肿瘤微环境及决定免疫应答中的关键作用。

Abstract: CXCL10, an interferon-γ-inducible chemokine that attracts CXCR3⁺ T and NK cells, plays a critical role in shaping antitumor immunity, yet its prognostic significance and cellular origin in melanoma remain unclear. By integrating bulk RNA-seq data from TCGA with single-cell transcriptomic datasets from the TISCH database, we systematically characterized the expression patterns, prognostic value, immune associations, and biological context of CXCL10 in skin cutaneous melanoma (SKCM). High CXCL10 expression predicted significantly improved overall survival and delineated an interferon-driven, immune-active tumor phenotype enriched for cytotoxic and antigen-presentation signatures, whereas CXCL10-low tumors exhibited melanocytic lineage and pigmentation programs. Correlation analyses revealed strong associations between CXCL10 and immune effector genes, including CD8A, GZMB, PRF1, and HLA molecules, as well as immune checkpoints such as PDCD1 and CTLA4, indicating a coordinated adaptive immune activation. Single-cell analyses across three independent immunotherapy cohorts (GSE115978, GSE120575, and GSE123139) consistently demonstrated that CXCL10 is predominantly produced by tumor-associated macrophages and dendritic cells rather than tumor or lymphoid populations. Together, these findings identify CXCL10 as a robust biomarker of interferon-mediated immune activation and favorable prognosis in melanoma, highlighting the pivotal role of myeloid-derived CXCL10 in orchestrating an inflamed tumor microenvironment and guiding immunotherapeutic response.