在蕈样肉芽肿病（MF）中，恶性T淋巴细胞的增殖主要限制在皮肤中，这意味着恶性细胞对其特定的皮肤肿瘤微环境（TME）具有依赖性，包括与非恶性免疫和基质细胞、细胞因子和其他免疫调节因子的相互作用。为了探索这些相互作用，我们通过单细胞RNA测序对MF皮肤肿瘤的TME进行了全面的转录组分析。我们的分析确定了MF TME中细胞类型组成、细胞功能和细胞间相互作用，这些与健康皮肤和良性皮肤病的差异明显。尽管基因表达模式在患者样本之间是共同的，但在免疫和基质细胞中也观察到高水平的转录多样性，并且这些细胞与恶性T淋巴细胞之间存在着动态的相互作用和相互调控。这种异质性与细胞运输、基质相互作用、血管生成、免疫功能和代谢等过程有关，这些过程影响着癌细胞的生长、迁移和侵袭，以及抗肿瘤免疫。通过全面描述MF肿瘤中切皮环境中免疫和基质细胞的转录组，我们已经确定了所有肿瘤共同的功能失调模式，这些模式是寻找具有治疗潜力的候选物以及个体化疾病管理的重要资源。

Malignant T lymphocyte proliferation in mycosis fungoides (MF) is largely restricted to the skin, implying that malignant cells are dependent on their specific cutaneous tumor microenvironment (TME), including interactions with non-malignant immune and stromal cells, cytokines, and other immunomodulatory factors. To explore these interactions, we performed a comprehensive transcriptome analysis of the TME in advanced-stage MF skin tumors by single-cell RNA sequencing. Our analysis identified cell-type compositions, cellular functions, and cell-cell interactions in the MF TME that were distinct from those from healthy skin and benign dermatoses. While patterns of gene expression were common amongst patient samples, high transcriptional diversity was also observed in immune and stromal cells, with dynamic interactions and crosstalk between these cells and malignant T lymphocytes. This heterogeneity mapped to processes such as cell trafficking, matrix interactions, angiogenesis, immune functions, and metabolism that affect cancer cell growth, migration and invasion, as well as anti-tumor immunity. By comprehensively characterizing the transcriptomes of immune and stromal cell within the cutaneous microenvironment of individual MF tumors, we have identified patterns of dysfunction common to all tumors that represents a resource for identifying candidates with therapeutic potential as well as patient-specific heterogeneity that has important implications for personalized disease management.