CORRELATING THE TRANSCRIPTIONAL REGULATION OF uNK AND pNK CELLS WITH FUNCTIONAL MODALITIES THROUGH META-ANALYSIS APPROACH

Abstract

Natural killer cells form the first line of defense against the viral infections and tumor cells in the body. NK cells are present abundantly in the body in various organs covering primary and secondary lymphoid to non-lymphoid organs as well. Here, the two extremes, pNK and uNK have been discussed in detail. The differences in NK cells can be correlated to the expression of different transcriptional factors by them. Transcriptional factors play a key role in the regulation of NK cells functionality and it becomes important to understand the expression of different transcriptional factors by NK cells. Besides regulating NK cell development, transcription factors such as GATA-3 is involved in preventing infections such from Listeria monocytogenes. Studying the transcriptional factors would help in designing novel immunotherapeutics by modulating the expression of transcription factors in NK cells. The work focuses on correlating the transcriptional regulation of peripheral and uterine NK cells to functionality and then comparing the biological pathways involved in these NK cells in tumor microenvironment. Here, hepatocellular carcinoma (HCC) pNK cells would be used to carry out gene enrichment analysis with respect to the healthy pNK cells. Tumor microenvironment such as of HCC provides an amalgamation of multiple pathways ultimately covering all of them and providing insights about the pathways that are downregulated or upregulated in that environment. NK cells in HCC have been found to have a downregulation of cytotoxic pathways such as interferon-gamma/alpha compared to the healthy NK cells. This downregulation of the cytotoxic pathways results in progression of the cancer. Therefore, the gene-enrichment analysis for understanding the functionality of NK cells in different environment is of importance.