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 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 anti-tumor 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 anti-tumor Ag responses. TCRseq and tumor-Ag tetramer staining characterized the recirculation pattern of the anti-tumor 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.