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.
[1]Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China;
[2]Xuzhou Med Univ, Affiliated Hosp, Huaian Peoples Hosp 2, Dept Rehabil, Huaian, Peoples R China;
[3]Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Urol, Shanghai 200020, Peoples R China;
[4]Yangzhou Univ, Affiliated Hosp 6, Dept Lab Med, Taizhou 225400, Jiangsu, Peoples R China;
[5]Bengbu Med Coll, Affiliated Mixing Hosp, Dept Lab Med, Taizhou 225400, Jiangsu, Peoples R China;
[6]Sun Yat Sen Univ, Affiliated Hosp 1, Dept Orthoped, 58 Zhongshan Second Rd, Guangzhou 510080, Guangdong, Peoples R China;
[7]Fudan Univ, Sch Pharm, Dept Pharmacol, Shanghai 201203, Peoples R China;
[8]Fudan Univ, Minhang Hosp, Shanghai 201203, Peoples R China
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