摘要

Rationale: Previous studies have implicated the functions of stromal interaction molecule 1 (STIM1) in immunity and malignancy, however, the specificity and effects of STIM1 expression in malignant and non-malignant cells in the tumor microenvironment are unclear. Methods: In the current study, we posed two central questions: (1) does STIM1 expression elicit different cellular programs in cell types within the melanoma tumor microenvironment (2) whether the expression of STIM1 and STIM1-coexpressed genes (SCGs) serve as prognostic indicators of patient’s outcomes? To answer these questions, we dissected cell-specific STIM1-associated cellular programs in diverse cell types within the melanoma tumor microenvironment by measuring cell-type specificity of STIM1 expression and SCGs. Results: 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 STIM1 expression. In contrast to malignant cells, STIM1 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. Conclusions: Overall, our results provide an integrated biological framework for understanding the functional and clinical consequences of cell-specific STIM1 expression in melanoma.
原文英語
頁(從 - 到)5092-5106
頁數15
期刊Theranostics
11
發行號11
DOIs
出版狀態已發佈 - 三月 2021

ASJC Scopus subject areas

  • 醫藥(雜項)
  • 藥理學、毒理學和藥劑學(雜項)

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