Naturally Killing the Silent Killer: NK Cell-Based Immunotherapy for Ovarian Cancer

Abstract

Ovarian cancer (OC) is diagnosed in ~22,000 women in the US each year and kills 14,000 of them. Often, patients are not diagnosed until the later stages of disease, when treatment options are limited, highlighting the urgent need for new and improved therapies for precise cancer control. An individual's immune function and interaction with tumor cells can be prognostic of the response to cancer treatment. Current emerging therapies for OC include immunotherapies, which use antibodies or drive T cell-mediated cancer recognition and elimination. In OC, these have been limited by adverse side effects and tumor characteristics including inter- and intra-tumoral heterogeneity, lack of targetable antigens, loss of tumor human leukocyte antigen expression, high levels of immunosuppressive factors, and insufficient immune cell trafficking. Natural killer (NK) cells may be ideal as primary or collateral effectors to these nascent immunotherapies. NK cells exhibit multiple functions that combat immune escape and tumor relapse: they kill targets and elicit inflammation through antigen-independent pathways and detect loss of HLA as a signal for activation. NK cells are efficient mediators of tumor immune surveillance and control, suppressed by the tumor microenvironment and rescued by immune checkpoint blockade. NK cells are regulated by a variety of activating and inhibitory receptors and already known to be central effectors across an array of existing therapies. In this article, we highlight interactions between NK cells and OC and their potential to change the immunosuppressive tumor microenvironment and participate in durable immune control of OC.

Obesity-Associated Alterations of Natural Killer Cells and Immunosurveillance of Cancer

“…Besides the application of NK cell stimulating cytokines, the treatment of cancer patients with antibodies targeting inhibitory NK cell receptors or agonists of activating NK cell receptors were used to increase the number and functionality of NK cells. Very recently, a review by Nersesian et al demonstrated the success of NK cell-based therapy in patients with ovarian cancer; however, aspects of obesity were not touched (180). In addition, NK cell adoptive transfer therapies for cancer patients using allogenic blood NK cells, stem cell-derived NK cells, or different NK cell lines exhibited promising effects in the treatment of several cancer types, whereas only limited clinical benefits were observed in cancer patients who received an adoptive transfer of autologous NK cells (181)(182)(183).…”

Highly efficient serum-free manipulation of miRNA in human NK cells without loss of viability or phenotypic alterations is accomplished with TransIT-TKO

“…chimeric antigen receptors or cytokines), for fit-for-purpose applications in immunotherapy [21]. Despite their advantages NK cell-based clinical trials have yielded heterogeneous results, likely reflecting further obstacles, such as immunosuppression in a tumor microenvironment, that hinder their reactivity [43,44]. Analysis of miRNA transcriptomes from NK cells derived from peripheral blood, cord blood, and uterine decidua reveal significant differences in miRNA profiles, suggesting that miRNA may help to calibrate and tailor NK cell effector functions.…”

CLDN6 and CLDN10 are Associated with Immune Infiltration of Ovarian Cancer: A Study of Claudin Family

“…Growing evidence shown that the presence of TILs may improve clinical outcome of ovarian cancer patients [40] . Immune cell-based immunotherapy [30] including NK Cells [31] and dendritic cells [32] play important roles in the treatment of ovarian cancer. Our results suggested that CLDN6 may be involved in tumor immune evasion, and may represent ideal candidate for immunotherapy in ovarian cancer.…”

“…Studies have shown that the in ltration of these immune cells in the tumor microenvironment is related to the tumor immunotherapy response [29] . Immune cell-based immunotherapy [30] including NK Cells [31] and dendritic cells [32] play important roles in the treatment of ovarian cancer. Taken these analyses together, our research showed that CLDN6 and CLDN10 may play important roles in immunotherapy in the future.…”