Development and Validation of a Prognostic Risk Model Based on Nature Killer Cells for Serous Ovarian Cancer

Abstract

Nature killer (NK) cells are increasingly considered important in tumor microenvironment, but their role in predicting the prognosis of ovarian cancer has not been revealed. This study aimed to develop a prognostic risk model for ovarian cancer based on NK cells. Firstly, differentially expressed genes (DEGs) of NK cells were found by single-cell RNA-sequencing dataset analysis. Based on six NK-cell DEGs identified by univariable, Lasso and multivariable Cox regression analyses, a prognostic risk model for serous ovarian cancer was developed in the TCGA cohort. This model was then validated in three external cohorts, and evaluated as an independent prognostic factor by multivariable Cox regression analysis together with clinical characteristics. With the investigation of the underlying mechanism, a relation between a higher risk score of this model and more immune activities in tumor microenvironment was revealed. Furthermore, a detailed inspection of infiltrated immunocytes indicated that not only quantity, but also the functional state of these immunocytes might affect prognostic risk. Additionally, the potential of this model to predict immunotherapeutic response was exhibited by evaluating the functional state of cytotoxic T lymphocytes. To conclude, this study introduced a novel prognostic risk model based on NK-cell DEGs, which might provide assistance for the personalized management of serous ovarian cancer patients.

Cyclooxygenase-2 Blockade Is Crucial to Restore Natural Killer Cell Activity before Anti-CTLA-4 Therapy against High-Grade Serous Ovarian Cancer

“…Hence, we wanted to evaluate if the PTGS2 / CTLA4 ratio also determines the infiltration and cytotoxic capacity estimate in HGSOC. For this, we considered the recent publication by Zhang et al [ 54 ]. In that work, the authors proposed several genes associated with risk prognosis models through differential expression analysis.…”

CAR memory–like NK cells targeting the membrane proximal domain of mesothelin demonstrate promising activity in ovarian cancer

“…The multiple mechanisms of killing, low risk of CRS, GvHD, and neurotoxicity make NK cells an attractive platform for adoptive cell therapy-based approaches, and their translation in early clinical trials has demonstrated safety and promising preliminary results in multiple cancers. In EOC, the presence of NK cells correlates with improved survival, and a prognostic risk model based on differentially expressed genes of NK cells in EOC samples has recently been reported, further underscoring the importance of NK cellmediated antitumor activity (16,17).…”