Targeting the tumour immune microenvironment for cancer therapy in human gastrointestinal malignancies

Gastrointestinal (GI) cancer is a malignancy of the GI tract and accessory digestive organs. GI cancer patients develop resistance to chemotherapy, targeted therapy drugs and immune therapies. Although immune checkpoint inhibitors have shown promising clinical results in melanoma, etc., immune checkpoint blockade responds in only a subset of colorectal cancer (CRC) patients with microsatellite instability-high (MSI-H) tumours. The tumour immune microenvironment (TIME) has a dynamic nature during malignant progression to which all the cells in the TIME contribute. Recent studies have highlighted the role of the TIME in the therapy resistance of cancer. Immune suppressive cells, such as tumour-associated macrophages, regulatory T cells, and myeloid derived suppressor cells, consist of a suppressive TIME to resist immune reactions. Combination approaches used to target the TIME, such as radiotherapy, chemotherapy, targeted therapy combined with checkpoint blockers or immune cell therapy, in addition to mono-immunotherapy, may provide better therapy responses. This review provides an analysis of recent developments regarding the role of the TIME in malignant progression, immunotherapy and the development of drug resistance in GI tract cancer, especially CRC, as well as approaches to overcome microenvironment-mediated resistance.