Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
J Invest Dermatol. 2024 Feb;144(2):331-340.e2. doi: 10.1016/j.jid.2023.05.030. Epub 2023 Aug 5.
Mycosis fungoides with large-cell transformation (MF-LCT) occurs in a minor proportion of aggressive lesions, which express CD30 similar to primary cutaneous anaplastic large-cell lymphoma (pcALCL). We investigated the differences in spatially resolved transcriptome profiles of MF-LCT and pcALCL using CD30 morphology markers and 28 and 24 regions of interest (ROIs) in MF-LCT and pcALCL, respectively. Differentially expressed genes, pathway analysis, and immune-cell deconvolution by selective analysis of CD30-positive tumor cells and CD30-negative extratumoral areas were undertaken. In CD30-positive ROIs of MF-LCT, 190 differentially expressed genes were upregulated (29 were directly or indirectly associated with extracellular matrix remodeling), whereas 255 differentially expressed genes were downregulated, compared with those of pcALCL. Except for cornified envelope formation and keratinization, all six pathways enriched in CD30-positive ROIs of MF-LCT were associated with extracellular matrix remodeling. In CD30-positive ROIs in MF-LCT compared with those in pcALCL, immune-cell deconvolution revealed significantly increased fibroblasts and M2 macrophages (P = 0.012 and P = 0.023, respectively) but decreased M1 macrophages (P = 0.031). In CD30-negative ROIs in MF-LCT compared with those in pcALCL, memory B (P = 0.021), plasma (P = 0.023), and CD8 memory T (P = 0.001) cells significantly decreased, whereas regulatory T cells (P = 0.024) increased. Predomination of extracellular matrix remodeling pathways and immunosuppressive microenvironment in MF-LCT indicates pathophysiological differences between MF-LCT and pcALCL.
蕈样肉芽肿伴大细胞转化（MF-LCT）发生于侵袭性皮损中的一小部分，其表达 CD30，类似于原发性皮肤间变大细胞淋巴瘤（pcALCL）。我们使用 CD30 形态标志物和 MF-LCT 中的 28 个和 pcALCL 中的 24 个感兴趣区域（ROI），研究了 MF-LCT 和 pcALCL 空间分辨转录组谱的差异。进行了差异表达基因、通路分析和通过选择性分析 CD30 阳性肿瘤细胞和 CD30 阴性肿瘤外区域进行免疫细胞去卷积。在 MF-LCT 的 CD30 阳性 ROI 中，有 190 个差异表达基因上调（29 个直接或间接与细胞外基质重塑有关），而与 pcALCL 相比，有 255 个差异表达基因下调。除了角质形成和角化外，MF-LCT 的 CD30 阳性 ROI 中富集的所有 6 个通路都与细胞外基质重塑有关。与 pcALCL 相比，MF-LCT 的 CD30 阳性 ROI 中的免疫细胞去卷积显示成纤维细胞和 M2 巨噬细胞显著增加（P=0.012 和 P=0.023），而 M1 巨噬细胞减少（P=0.031）。与 pcALCL 相比，MF-LCT 的 CD30 阴性 ROI 中记忆 B（P=0.021）、浆细胞（P=0.023）和 CD8 记忆 T（P=0.001）细胞显著减少，而调节性 T 细胞（P=0.024）增加。MF-LCT 中细胞外基质重塑通路和免疫抑制微环境的优势表明 MF-LCT 和 pcALCL 之间存在病理生理学差异。
