The implication of resting natural killer cells in mesothelioma.

Abstract

e20099 Background: Mesothelioma is a rare and aggressive cancer strongly associated with asbestos exposure. It is typically an incurable disease, with treatment focusing on palliative chemotherapy, radiation, and immunotherapy. Novel insights into the tumor microenvironment have provided a unique perspective on treatment options and prognosis. Resting natural killer (NK) cells are an inactive form of NK cells that are less cytotoxic than their activated counterparts. NK cells typically function by producing cytokines to inhibit tumor progression and releasing chemicals to destroy malignant cells. The inactive form of NK cells serves as a reservoir that can be rapidly recruited and activated in response to tumor-derived signals. Resting NK cells have been shown to play a role in the overall survival of mesothelioma, offering a potential avenue for innovative treatment strategies. Methods: RNA sequencing data from The Cancer Genome Atlas (TCGA) in mesothelioma patients was analyzed. Immune cell fractions in tumor samples were identified using CIBERSORT which is a computational tool used in estimating relative abundance of different cell types in a given tissue sample. Radiant by Shiny was utilized to demonstrate a linear regression between overall survival and various immune cell types. This analysis included memory T cells, B cells, plasma cells, NK cells, monocytes, macrophages, and dendritic cells, in both their active and inactive forms. Results: Natural killer cells were analyzed through linear regression and found to be independently associated with overall survival in malignant mesothelioma. The analysis yielded a p-value of 0.039 and a correlation coefficient of +164.598, indicating a positive relationship between the presence of inactive NK cells and overall survival in mesothelioma. Conclusions: The presence of inactive NK cells in the tumor microenvironment of malignant mesothelioma is associated with increased overall survival. While active NK cells have been linked to prolonged survival in other cancers, such as colorectal, renal, and squamous cell carcinomas, this study emphasizes the inactive form of NK cells in mesothelioma. Studies have found that gemcitabine, when used for mesothelioma, can increase the number of responding NK cells, thus highlighting the importance of said cells in the tumor microenvironment. Enhancing NK cell activity using cytokines such as IL-7, VEGF, or TNF-alpha may offer a novel therapeutic approach with a more favorable safety profile. However, significant challenges remain in managing immunotherapies and mitigating their potential consequences.