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Mol Cancer. 2018 Feb 15;17(1):32. doi: 10.1186/s12943-018-0814-0.

Engineering chimeric antigen receptor-T cells for cancer treatment.

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Department of Hematology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, China.
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, 94305-5117, USA.
Department of Neurosurgery, Xiangya Hospital, Central south University, Changsha, Hunan, 410008, China.
Lab of Neuro-Oncology, Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-repair and Regeneration in Central Nervous System, Tianjin, China.
Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, China.


Intratumor heterogeneity of tumor clones and an immunosuppressive microenvironment in cancer ecosystems contribute to inherent difficulties for tumor treatment. Recently, chimeric antigen receptor (CAR) T-cell therapy has been successfully applied in the treatment of B-cell malignancies, underscoring its great potential in antitumor therapy. However, functional challenges of CAR-T cell therapy, especially in solid tumors, remain. Here, we describe cancer-immunity phenotypes from a clonal-stromal-immune perspective and elucidate mechanisms of T-cell exhaustion that contribute to tumor immune evasion. Then we assess the functional challenges of CAR-T cell therapy, including cell trafficking and infiltration, targeted-recognition and killing of tumor cells, T-cell proliferation and persistence, immunosuppressive microenvironment and self-control regulation. Finally, we delineate tumor precision informatics and advancements in engineered CAR-T cells to counteract inherent challenges of the CAR-T cell therapy, either alone or in combination with traditional therapeutics, and highlight the therapeutic potential of this approach in future tumor precision treatment.


Cancer immunotherapy; Chimeric antigen receptor (CAR) T cell therapy; Intratumor heterogeneity; T-cell exhaustion; Tumor ecosystem

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