Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment. Oral squamous cell carcinoma (OSCC), a representative hypoxic tumor, has a heterogeneous internal metabolic environment. To clarify the relationship between different metabolic regions and the tumor immune microenvironment (TME) in OSCC, Single cell (SC) and spatial transcriptomics (ST) sequencing of OSCC tissues were performed. The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data. The metabolic activity of each spot was calculated using scMetabolism, and k-means clustering was used to classify all spots into hyper-, normal-, or hypometabolic regions. CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others. Through CellPhoneDB and NicheNet cell-cell communication analysis, it was found that in the hypermetabolic region, fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts (iCAFs), and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12. The secretion of CXCL12 recruits regulatory T cells (Tregs), leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment. This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC, ST and TCGA bulk data, and highlights potential targets for therapy.

肿瘤进展与肿瘤组织代谢和微环境重塑密切相关。口腔鳞状细胞癌（OSCC）是一种代表性的缺氧肿瘤，具有异质的内部代谢环境。为了阐明 OSCC 中不同代谢区域与肿瘤免疫微环境 (TME) 之间的关系，对 OSCC 组织进行了单细胞 (SC) 和空间转录组 (ST) 测序。ST 数据中 TME 的比例是使用 SC 和 GSE103322 数据通过 SPOTlight 反卷积获得的。使用 scMetabolism 计算每个点的代谢活性，并使用 k 均值聚类将所有点分类为高代谢、正常或低代谢区域。代谢亢进区域的 CD4T 细胞浸润和 TGF-β 表达高于其他区域。通过CellPhoneDB和NicheNet细胞间通讯分析发现，在高代谢区域，成纤维细胞可以利用上皮细胞糖酵解产生的乳酸转化为炎性癌症相关成纤维细胞（iCAFs），并且iCAFs中HIF1A表达增加促进CXCL12的转录表达。CXCL12的分泌招募调节性T细胞（Treg），导致微环境中Treg浸润和TGF-β分泌增加，促进肿瘤免疫抑制微环境的形成。本研究使用 SC、ST 和 TCGA 批量数据描绘了 OSCC 中上皮细胞 - iCAF - Tregs 的协调工作轴，并强调了潜在的治疗靶点。