Omics analysis of uveal melanoma: Leukocyte gene signatures reveal novel survival distinctions and indicate a prognostic role for cytolytic activity scoring

Objective: The significant metastatic potential of uveal melanoma (UVM) lends to high mortality. Even with successful local tumor treatment, many patients will develop metastatic disease. The present study aims to elucidate the relationship between tumor-infiltrating immune cell (TIIC) diversity and survival to identify potential therapeutic targets and improve UVM prognosis. Methods: Bulk deconvolution was used to determine the relative proportions of 22 hematopoietic TIIC from 80 UVM tumor samples. Cytolytic activity (CYT) was determined, and associated survival probabilities were mined using time-to-event data. Nominal P-values were subjected to FDR correction. Results: High relative abundance of tumor-infiltrating naïve B cells, resting memory CD4+ T cells, and monocytes correlated with better overall and disease-free survival probability. Low relative abundance of CD8+ T cells correlated with better overall survival and disease-free survival probability. CYT correlated positively with relative abundance of naïve B cells, resting memory CD4+ T cells, and monocytes. CYT correlated negatively with relative abundance of CD8+ T cells. Conclusion: Infiltrating naïve B cells, resting memory CD4+ T cells, monocytes, and CD8+ T cells are potential therapeutic targets in UVM that warrant further investigation. High CYT estimates associate with worse UVM survival outcomes.