Single-cell Melanoma Transcriptomes Depicting Functional Versatility and Clinical Implications of STIM1 in the Tumor Microenvironment

Previous studies have implicated the functions of stromal interaction molecule 1 () in immunity and malignancy, however, the specificity and effects of expression in malignant and non-malignant cells in the tumor microenvironment are unclear. In the current study, we posed two central questions: (1) does expression elicit different cellular programs in cell types within the melanoma tumor microenvironment (2) whether the expression of and -coexpressed genes (SCGs) serve as prognostic indicators of patient's outcomes? To answer these questions, we dissected cell-specific -associated cellular programs in diverse cell types within the melanoma tumor microenvironment by measuring cell-type specificity of expression and SCGs. A distinct set of SCGs was highly affected in malignant melanoma cells, but not in the other cell types, suggesting the existence of malignant-cell-specific cellular programs reflected by expression. In contrast to malignant cells, expression appeared to trigger universal and non-specific biological functions in non-malignant cell types, as exemplified by the transcriptomes of macrophages and CD4 T regulatory cells. Results from bioinformatic analyses indicated that SCGs in malignant cells may alter cell-cell interactions through cytokine/chemokine signaling and/or orchestrate immune infiltration into the tumor. Moreover, a prognostic association between SCGs in CD4 T regulatory cells and patient's outcomes was identified. However, we didn't find any correlation between SCGs and responsiveness of immunotherapy. Overall, our results provide an integrated biological framework for understanding the functional and clinical consequences of cell-specific expression in melanoma.