| Autor: |
Yuxin Chen, Meng Wang, Shuxin Huang, Lulu Han, Ying Cai, Xiaodi Xu, Shuwen Sun, Zhaokai Chen, Junze Chen, Jiatian Yu, Hongwei Du, Huizhong Li, Junnian Zheng, Bo Ma, Gang Wang |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Pharmacological Research, Vol 210, Iss , Pp 107506- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
1096-1186 |
| DOI: |
10.1016/j.phrs.2024.107506 |
| Popis: |
Lack of biopsies after treatment, especially in solid tumors, restricts the understanding of chimeric antigen receptor (CAR)-T cells -related characteristic in vivo, thus hindering the development of strategies to improve CAR-T cells efficacy. Here, we applied nineteen individual single-cell RNA sequencing (scRNA-seq) data from clinical samples of digestive cancers to explore the characteristics of tumor-infiltrating T cells (TILs) to identify effective targets which might be benefit for enhancing the function of CAR-T cells. The data showed that natural killer cell granule protein 7 (NKG7) was overexpressed in TILs and positively associated with anti-PD1 or anti-CTLA4 therapy in digestive cancers. Subsequently, we found that ectopic expression of NKG7 significantly improved the cytotoxicity of B7H3-targeting CAR-T cells to B7H3-positive digestive cancer cells (MKN45, Huh7, HuCCT-1, SW620 and PANC-1 cells), as well as promoted the TNF-α and IL-2 expression. Furthermore, in a CD19-targeting CAR-T model, the therapeutic efficacy was also found increased after NKG7 overexpression. Mechanically, NKG7 preserved surface CAR expression and promoted CAR-T cell proliferation after exposing to relative tumor antigen. These results indicated that it may be feasible to explore single-cell sequencing data of clinical tumor samples to find strategies to improve CAR-T function, and that ectopic expression of NKG7 is an effective strategy to improve the therapeutic efficacy of CAR-T cells against tumors. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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