The prognostic landscape of adaptive immune resistance signatures and infiltrating immune cells in the tumor microenvironment of uveal melanoma

Abstract

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults and has a high mortality rate. Tumor microenvironment (TME) is crucial in controlling and influencing the behavior of malignant tumors. Thus, illustrating the prognostic values of adaptive immune resistance signatures and infiltrating immune cells in the TME of UM may provide scientific rationales for immunotherapy. In this study, the gene expression data of 80 primary UM and 103 primary skin cutaneous melanoma (SKCM) samples with relevant clinical information were obtained from The Cancer Genome Atlas (TCGA) database. The TME was analyzed by the xCell, EPIC, ESTIMATE and TIMER algorithms. The relationships and prognostic values of immune infiltrates and mutated genes were further investigated. We found that primary UM and primary SKCM exhibited distinct TMEs. Higher levels of infiltrating stromal and immune cells in UM were related to more aggressive biology and poor prognosis. Increased CD8⁺ T cell level, as well as several adaptive immune resistance markers, was a predictive factor of poor prognosis in UM. Furthermore, some common mutations of UM were associated with its TME. This study analyzed the immune landscape of adaptive immune resistance signatures and infiltrating immune cells in the TME of UM. Identification of these immune-related biomarkers may thus enable the prediction of prognosis and the selection of optimal immunotherapy strategies in UM.

Keywords: Adaptive immune resistance; Infiltrating immune cells; Tumor microenvironment; Uveal melanoma.