Francesca Lucibello, Ana I Lalanne, Anne-Laure Le Gac, Abdoulaye Soumare, Setareh Aflaki, Joanna Cyrta, Lea Dubreuil, Martin Mestdagh, Marion Salou, Alexandre Houy, Christina Ekwegbara, Camille Jamet, Sophie Gardrat, Anais Le Ven, Karine Bernardeau, Nathalie Cassoux, Alexandre Matet, Denis Malaise, Gaelle Pierron, Sophie Piperno-Neumann, Marc-Henri Stern, Manuel Rodrigues, Olivier Lantz
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引用次数: 0
摘要
葡萄膜黑色素瘤(UM)是最常见的眼癌。3 号染色体(M3)缺失与高转移风险有关。与低风险的 3 号染色体缺失(D3)肿瘤相比,M3 肿瘤的 T 淋巴细胞浸润更多,这与其他肿瘤类型形成鲜明对比,后者的 T 细胞浸润与较好的预后有关。这些 T 细胞是否代表一种抗肿瘤反应,以及这些 T 细胞如何在眼部被激活,这些都是未知数。在这里,我们描述了浸润原发性 UMs 的 T 细胞的特征。M3肿瘤中的CD8+细胞和Treg细胞比D3肿瘤中的更多。CD39+PD-1+CD8+T细胞在M3肿瘤中富集,表明对肿瘤抗原(Ag)有特异性反应,这一点已通过HLA-A2:Melan-A四聚体得到证实。T细胞的scRNAseq-VDJ分析表明CD39+PD1+CD8+克隆扩增数量较多,表明原位抗肿瘤Ag反应。TCRseq和肿瘤-Ag四聚体染色描述了M3和D3肿瘤中抗肿瘤反应的再循环模式。因此,肿瘤-Ag 反应发生在局部 UMs 中,这就提出了在没有已知淋巴引流的情况下的启动机制问题。
Divergent local and systemic antitumor response in primary uveal melanomas.
Uveal melanoma (UM) is the most common cancer of the eye. The loss of chromosome 3 (M3) is associated with a high risk of metastases. M3 tumors are more infiltrated by T-lymphocytes than low-risk disomic-3 (D3) tumors, contrasting with other tumor types in which T cell infiltration correlates with better prognosis. Whether these T cells represent an antitumor response and how these T cells would be primed in the eye are both unknown. Herein, we characterized the T cells infiltrating primary UMs. CD8+ and Treg cells were more abundant in M3 than in D3 tumors. CD39+PD-1+CD8+ T cells were enriched in M3 tumors, suggesting specific responses to tumor antigen (Ag) as confirmed using HLA-A2:Melan-A tetramers. scRNAseq-VDJ analysis of T cells evidenced high numbers of proliferating CD39+PD1+CD8+ clonal expansions, suggesting in situ antitumor Ag responses. TCRseq and tumor-Ag tetramer staining characterized the recirculation pattern of the antitumor responses in M3 and D3 tumors. Thus, tumor-Ag responses occur in localized UMs, raising the question of the priming mechanisms in the absence of known lymphatic drainage.
期刊介绍:
Since its establishment in 1896, the Journal of Experimental Medicine (JEM) has steadfastly pursued the publication of enduring and exceptional studies in medical biology. In an era where numerous publishing groups are introducing specialized journals, we recognize the importance of offering a distinguished platform for studies that seamlessly integrate various disciplines within the pathogenesis field.
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