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Enhancing CAR-T cell efficacy in solid tumors by targeting the tumor microenvironment

期刊

CELLULAR & MOLECULAR IMMUNOLOGY
卷 18, 期 5, 页码 1085-1095

出版社

CHIN SOCIETY IMMUNOLOGY
DOI: 10.1038/s41423-021-00655-2

关键词

CAR-T; Tumor; Microenvironment

资金

  1. National Natural Science Foundation of China [31821003]
  2. Tsinghua-Peking Center for Life Sciences

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CAR-T cell therapy has shown successful outcomes in hematological malignancies but faces challenges in treating solid tumors due to immunosuppressive mechanisms in the tumor microenvironment. This review summarized inhibitory factors affecting CAR-T cell function and discussed strategies to enhance CAR-T cell efficacy in solid tumor treatment by targeting these barriers.
Chimeric antigen receptor (CAR)-T cell therapy has achieved successful outcomes against hematological malignancies and provided a new impetus for treating solid tumors. However, the efficacy of CAR-T cells for solid tumors remains unsatisfactory. The tumor microenvironment has an important role in interfering with and inhibiting the effector function of immune cells, among which upregulated inhibitory checkpoint receptors, soluble suppressive cytokines, altered chemokine expression profiles, aberrant vasculature, complicated stromal composition, hypoxia and abnormal tumor metabolism are major immunosuppressive mechanisms. In this review, we summarize the inhibitory factors that affect the function of CAR-T cells in tumor microenvironment and discuss approaches to improve CAR-T cell efficacy for solid tumor treatment by targeting those barriers.

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