Immunotherapy in gastrointestinal cancers: current strategies and future directions - a literature review.

Introduction: The National Cancer Institute defines the disease of "cancer" as a group of disorders in which aberrant cells proliferate uncontrollably and have the potential to infiltrate neighboring tissues. It is well established that cancer remains a significant etiology contributing to worldwide mortality. Gastrointestinal (GI) neoplasms are a type of cancer that affects the digestive system and adds to the total cancer burden. Conventionally, several therapies have been employed, such as radiation and chemotherapy; nevertheless, their adverse effects have prompted the need for an improved therapeutic alternative. Immunotherapy thus became a notable medium of treatment for several malignancies, including tumors of the GI tract. Aim: This comprehensive review seeks to provide insight on future directions and prospective therapies under development, as well as information regarding the present strategies utilized to mitigate one of the primary forms of cancer, GI cancer. Methods: A detailed analysis of the existing literature on GI cancers has been conducted. Several databases were employed to gather this information, mainly PubMed/MEDLINE. Different aspects of the disease were considered when searching the databases to provide a comprehensive review of the current and future strategies being incorporated to mitigate the negative consequences of this disease. Results: Many strategies are being used currently, and some are still under development. These comprise the usage of immune checkpoint inhibitors (ICIs), cytokine therapy, cancer vaccines, oncolytic viruses, and adoptive cell therapy. For instance, various monoclonal antibodies have been developed to inhibit the immunomodulatory effects of programmed death-1 and programmed death-1 ligand. There are also results of several clinical trials showing significant benefits and many changes are introduced to make the best of these strategies and minimize the challenges to group sizes. These challenges include overcoming the tumor's immunosuppressive environment, finding suitable predictive biomarkers, and reducing the adverse effects. Additionally, several novel immunotherapeutic approaches, such as chimeric antigen receptor T-cell (CAR-T) therapy, are being studied. In 2017, the US FDA approved the use of two CAR-T therapies, which marks a major milestone following extensive research and clinical trials. New approaches such as toll-like receptor-directed and helminth-based immunotherapies are being developed for the treatment of GI cancers as well. These therapies, along with targeted treatments, represent the future of immunotherapy in GI cancers. Conclusion: Immunotherapy plays a significant role in the different types of GI cancers. However, optimizing these treatments will require overcoming barriers such as immune resistance, minimizing side effects, and improving the selection of patients through biomarkers. Continued research into these novel therapies and the mechanisms of immune modulation will be key to maximizing the therapeutic benefits of immunotherapy in the future.