Natural killer (NK) cells are important lymphocytes of the innate immunological defense against cancer. Based on their molecular and functional phenotypes NK cells are categorized in two main subtypes known as CD56 dim and CD56 bright, with distinct transcriptomes profiles. Additionally, transcriptomic alterations may arise in response to different stimuli or milieu, ultimately affecting the NK cell behavior. Herein, RNA sequencing was carried out to characterize the transcriptomic profile of NK cells present in epithelial ovarian cancer (EOC)-associated ascites. Two bulk RNA sequencing datasets of isolated NK cells were analyzed; one generated from sampling of patients assisted at the Women's Hospital of the University of Campinas (CAISM-Unicamp, Brazil) and the other made available at Gene Expression Omnibus database (GSE153713). Results identified 2829 differentially expressed genes (DEG ≥2 folds). RNA expression of genes encoding molecules associated with cytotoxic function ( NCR1, KLRK1, GZMB, PRF1) and maturation markers ( CLIC3, LAIR2, SPON2, CD160) were significantly downregulated in ascites NK cells. Alternatively, upregulated genes ( ICAM1, GZMK, IL18, IFNγ among others) strengthen to the ascites NK cells a transcriptomic profile consistent with the CD56 bright subtype. Finally, 120 upregulated genes were identified as highly correlated with the NCAM1/ FCGR3A expression ratio (ρ ≥0.7). Overall, these genes were interpreted as involved in suppression of signal transduction and intracellular signaling pathways, particularly redirecting the classical MAPK cascade to the p38MAPK. The transcriptomic profile of ascites NK cells included alterations consistent with lack of conventional blood cytotoxic cell characteristics, combined with an immature/secretory-like profile, assigned to the CD56 bright subtype of NK cells.
Souza-Araújo et al. (Thu,) studied this question.
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