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  • Lucibello, Francesca; Lalanne, Ana I; Le Gac, Anne-Laure; Soumare, Abdoulaye; Aflaki, Setareh; Cyrta, Joanna; Dubreuil, Lea; Mestdagh, Martin; Salou, Marion; Houy, Alexandre; Ekwegbara, Christina; Jamet, Camille; Gardrat, Sophie; Le Ven, Anais; Bernardeau, Karine; Cassoux, Nathalie; Matet, Alexandre; Malaise, Denis; Pierron, Gaelle; Piperno-Neumann, Sophie; Stern, Marc-Henri; Rodrigues, Manuel; Lantz, Olivier

    The Journal of experimental medicine, 06/2024, Letnik: 221, Številka: 6
    Journal Article

    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.