英国威康桑格研究所Muzlifah Haniffa等研究人员合作发现，皮肤T细胞淋巴瘤图谱揭示在富含B细胞的肿瘤微环境中得到支持的恶性T_H2细胞。相关论文于2024年11月18日在线发表在《自然—免疫学》杂志上。

研究人员对真菌性皮肤病型皮肤T细胞淋巴瘤（CTCL）患者的皮肤样本，进行了单细胞和空间转录组学分析，并与来自健康和发炎皮肤的人的皮肤细胞图谱数据集，进行了综合比较分析。研究人员揭示了恶性CTCL细胞通过共用T辅助2（T_H2）细胞免疫基因程序，以及肿瘤微环境的建模来支持其生存。

研究人员鉴定了MHC-II⁺成纤维细胞和树突状细胞，它们能够维持类似T_H2细胞的肿瘤细胞。CTCL肿瘤细胞与B细胞空间关联，形成类似三级淋巴结构的聚集体。

最后，研究人员验证了B细胞在CTCL中的富集，并发现其与疾病进展在三个独立患者队列中的相关性。这些研究结果为CTCL的诊断提供了辅助工具，提供了潜在的疾病分期生物标志物，并为治疗策略提供了参考。

研究人员表示，CTCL是一种潜在致命的T细胞克隆性恶性肿瘤，主要影响皮肤。CTCL最常见的类型为蕈样霉菌病（mycosis fungoides），其诊断较为困难，常导致治疗延误。

附：英文原文

Title: Cutaneous T cell lymphoma atlas reveals malignant TH2 cells supported by a B cell-rich tumor microenvironment

Author: Li, Ruoyan, Strobl, Johanna, Poyner, Elizabeth F. M., Balbaa, Aya, Torabi, Fereshteh, Mazin, Pavel V., Chipampe, Nana-Jane, Stephenson, Emily, Ramrez-Sustegi, Ciro, Shanmugiah, Vijaya Baskar Mahalingam, Gardner, Louis, Olabi, Bayanne, Coulthard, Rowen, Botting, Rachel A., Zila, Nina, Prigmore, Elena, Gopee, Nusayhah H., Chroscik, Marta A., Kritikaki, Efpraxia, Engelbert, Justin, Goh, Issac, Chan, Hon Man, Johnson, Harriet F., Ellis, Jasmine, Rowe, Victoria, Tun, Win, Reynolds, Gary, Yang, Dexin, Foster, April Rose, Gambardella, Laure, Winheim, Elena, Admane, Chloe, Rumney, Benjamin, Steele, Lloyd, Jardine, Laura, Nenonen, Julia, Pickard, Keir, Lumley, Jennifer, Hampton, Philip, Hu, Simeng, Liu, Fengjie, Liu, Xiangjun, Horsfall, David, Basurto-Lozada, Daniela, Grimble, Louise, Bacon, Chris M., Weatherhead, Sophie C., Brauner, Hanna, Wang, Yang, Bai, Fan, Reynolds, Nick J., Allen, Judith E., Jonak, Constanze, Brunner, Patrick M., Teichmann, Sarah A., Haniffa, Muzlifah

Issue&Volume: 2024-11-18

Abstract: Cutaneous T cell lymphoma (CTCL) is a potentially fatal clonal malignancy of T cells primarily affecting the skin. The most common form of CTCL, mycosis fungoides, can be difficult to diagnose, resulting in treatment delay. We performed single-cell and spatial transcriptomics analysis of skin from patients with mycosis fungoides-type CTCL and an integrated comparative analysis with human skin cell atlas datasets from healthy and inflamed skin. We revealed the co-optation of T helper 2 (TH2) cell-immune gene programs by malignant CTCL cells and modeling of the tumor microenvironment to support their survival. We identified MHC-II+ fibroblasts and dendritic cells that can maintain TH2 cell-like tumor cells. CTCL tumor cells are spatially associated with B cells, forming tertiary lymphoid structure-like aggregates. Finally, we validated the enrichment of B cells in CTCL and its association with disease progression across three independent patient cohorts. Our findings provide diagnostic aids, potential biomarkers for disease staging and therapeutic strategies for CTCL.

DOI: 10.1038/s41590-024-02018-1

Source: https://www.nature.com/articles/s41590-024-02018-1