Chimeric antigen receptor T-cell (CAR T-cell) and tumor-infiltrating lymphocytes (TILs) therapies in gastrointestinal malignancies: review of literature for clinical applications

Gastrointestinal malignancies (GI malignancies) have had a notoriously dismal prognosis throughout history. The primary therapeutic approaches to treat and manage GI malignancies are immunotherapy, radiotherapy, surgery, and chemotherapy, which may include monotherapy or a combination of these therapies to boost the effect. Nevertheless, the recurrence and metastasis rates remain elevated. In recent decades, immunotherapies have had a powerful impact when included in treatment regimens. In hematologic malignancy, chimeric antigen receptor T cells (CAR-T cell) have shown a promising anticancer impact as one of the immunotherapies. It gives a promising treatment option for solid tumors, including colorectal cancers. In recent clinical trials, the CAR-T cells showed a promising effect on pancreatic, colorectal, esophageal, hepatocellular, and gastric cancers. Tumor-infiltrating lymphocyte (TIL) therapy is another immunotherapy option with promising option for GI malignancies. Through the process of designing the TIL therapy, T cells are extracted and designed according to the nature of the GI malignancy. In this review, we addressed the clinical applications of both therapies while highlighting the challenges and possible strategies to overcome them. CAR T-cells and TIL therapies showed good responses with tolerable and acceptable side effects in treating GI malignancies such as pancreatic, colorectal, gastric, and hepatocellular cancers, while the immunosuppressive tumor microenvironment (TME) inhibiting the activity of immunotherapy and impeding its efficacy is a significant challenge.