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- Divergent local and systemic antitumor response in primary uveal melanomas
Divergent local and systemic antitumor response in primary uveal melanomas
Authors
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
Abstract
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.