Immunotherapy as a Therapeutic Strategy for Gastrointestinal Cancer-Current Treatment Options and Future Perspectives

Abstract

Gastrointestinal (GI) cancer constitutes a highly lethal entity among malignancies in the last decades and is still a major challenge for cancer therapeutic options. Despite the current combinational treatment strategies, including chemotherapy, surgery, radiotherapy, and targeted therapies, the survival rates remain notably low for patients with advanced disease. A better knowledge of the molecular mechanisms that influence tumor progression and the development of optimal therapeutic strategies for GI malignancies are urgently needed. Currently, the development and the assessment of the efficacy of immunotherapeutic agents in GI cancer are in the spotlight of several clinical trials. Thus, several new modalities and combinational treatments with other anti-neoplastic agents have been identified and evaluated for their efficiency in cancer management, including immune checkpoint inhibitors, adoptive cell transfer, chimeric antigen receptor (CAR)-T cell therapy, cancer vaccines, and/or combinations thereof. Understanding the interrelation among the tumor microenvironment, cancer progression, and immune resistance is pivotal for the optimal therapeutic management of all gastrointestinal solid tumors. This review will shed light on the recent advances and future directions of immunotherapy for malignant tumors of the GI system.

Keywords: cancer; cancer vaccine; checkpoint inhibitors; gastrointestinal tumors; immunotherapy; tumor microenvironment.

Figure 1

Schematic presentation of TME elements that induce immunosuppression, tumor progression, and metastasis. TME constitutes a surrounding stroma with a wide variety of cells, such as immune cells, fibroblasts, as well as many regulatory molecules, which are considered potential druggable targets. MDSC, B and T regulatory cells, TAMs, and cancer-associated fibroblasts (CAFs) have quite significant implications for cancer management, as they elicit an immunosuppressive effect that limits the efficacy of immunotherapeutic agents. TME immunosuppression is attributed to various molecules secreted by cancer cells, such as inhibitory checkpoints leading to the recruitment of immune cells, including MDSCs, T regulatory cells, and TAMs. This figure was created with BioRender.com, accessed on 14 May 2022 (agreement number UO23X0OEMQ).

Figure 2

Schematic presentation of immunotherapy modalities and their associated targets. There is a wide range of immunotherapeutic modalities that are introduced in the GI cancer management, including immune checkpoint inhibitors, adoptive cell transfer, chimeric antigen receptor (CAR)-T cell therapy, cancer vaccines, and/or combinations of all the aforementioned. This figure was created with BioRender.com (agreement number HP23X0I0W3).