Unraveling the Complexity of Immune Checkpoint Modulation in Gastrointestinal Malignancies
DOI:
https://doi.org/10.31580/3a0b5z06Keywords:
Cytokines, Gastrointestinal cancers, Gene expression, Immunological markers, Malignancies, Tumor microenvironmentAbstract
Gastrointestinal cancers are accountable for the highest mortality rates on a global scale, including gastric adenocarcinomas and hepatocellular carcinoma on a large scale. Tumor microenvironment has a vital role in influencing tumor behavior. Evading immune destruction prevents the immunological killing of cancer cells by T and B lymphocytes, macrophages and natural killer cells in the early stages of cancer progression. To determine the relative expression level of immunological markers and cytokines (CTLA-4, PD-1, PDL-1, LAG-3, IL-7R, and IL-12A) in tumor microenvironment of patients with gastrointestinal malignancies and their correlation with clinicopathological characteristics. Blood samples of gastrointestinal malignant patients were collected, followed by RNA extraction and cDNA synthesis for gene expression. The quantification of immune checkpoints and cytokines was carried out on the DNA using RT-qPCR. There is a significant increase in CTLA-4 expression in all the GIT cancers as compared to healthy controls. A slight increase in LAG-3 expression was observed in esopharyngeal carcinoma patients as compared to other GIT cancers. Downregulation of IL-7R and IL-12A was observed in all GIT cancers, however; gastric cancer shows a notable decrease in expression as compared to other GIT cancers and controls. Genetic expression of targeted immune checkpoints and cytokines is associated with cancer progression and helpful in unveiling the different mechanisms through which tumor microenvironment evades the immune system. This will lead to the development of effective immune checkpoint inhibitors as high-treatment efficacy drugs which activate the immune system, contributing to improved prognosis and therapeutic methods in aggressive tumor.
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