• Jiali Cheng, Lei Zhao, Yuanyuan Zhang, Yun Qin, Yuqi Guan, Tong Zhang, Chaohong Liu, and Jianfeng Zhou.
• Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China.
• Front Oncol. 2019 Jan 1; 9: 1237.

AbstractTaking advantage of the immune system to exert an antitumor effect is currently a novel approach in cancer therapy. Adoptive transfer of T cells engineered to express chimeric antigen receptors (CARs) targeting a desired antigen has shown extraordinary antitumor activity, especially in refractory and relapsed B-cell malignancies. The most representative in this respect, as well as the most successful example, is CD19 CAR T-cell therapy in B-cell acute lymphoblastic leukemia (B-ALL). However, with the widespread use of CAR T-cell therapy, problems of resistance and relapse are starting to be considered. This review provides a comprehensive picture of the mechanisms of resistance to CAR T-cell therapy from three aspects, namely, CAR T-cell factors, tumor factors, and tumor microenvironment factors, offering insights for improving CAR T-cell therapy.Copyright © 2019 Cheng, Zhao, Zhang, Qin, Guan, Zhang, Liu and Zhou.

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