Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602, USA.
Cells. 2022 Nov 16;11(22):3626. doi: 10.3390/cells11223626.
Chimeric antigen receptor (CAR) T cells are an exciting advancement in cancer immunotherapy, with striking success in hematological cancers. However, in solid tumors, the unique immunosuppressive elements of the tumor microenvironment (TME) contribute to the failure of CAR T cells. This review discusses the cell populations, cytokine/chemokine profile, and metabolic immunosuppressive elements of the TME. This immunosuppressive TME causes CAR T-cell exhaustion and influences failure of CAR T cells to successfully infiltrate solid tumors. Recent advances in CAR T-cell development, which seek to overcome aspects of the TME immunosuppression, are also reviewed. Novel discoveries overcoming immunosuppressive limitations of the TME may lead to the success of CAR T cells in solid tumors.
嵌合抗原受体 (CAR) T 细胞是癌症免疫疗法的一项重大进展，在血液癌症中取得了显著成功。然而，在实体肿瘤中，肿瘤微环境 (TME) 的独特免疫抑制因素导致 CAR T 细胞的失败。本文讨论了 TME 的细胞群体、细胞因子/趋化因子谱和代谢免疫抑制因素。这种免疫抑制的 TME 导致 CAR T 细胞衰竭，并影响 CAR T 细胞成功浸润实体肿瘤。还回顾了 CAR T 细胞开发方面的最新进展，这些进展旨在克服 TME 免疫抑制的某些方面。克服 TME 免疫抑制限制的新发现可能会使 CAR T 细胞在实体肿瘤中取得成功。
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