Details

Autor(en) / Beteiligte

• Yang, Li-Rong
• Li, Lin
• Meng, Ming-Yao
• Li, Tian-Tian
• Zhao, Yi-Yi
• Yang, Song-Lin
• Gao, Hui
• Tang, Wei-Wei
• Yang, Yang
• Yang, Li-Li
• Wang, Wen-Ju
• Liao, Li-Wei
• Hou, Zong-Liu

Titel

IL-7 promotes CD19-directed CAR-T cells proliferation through miRNA-98-5p by targeting CDKN1A

Ist Teil von

• International immunopharmacology, 2023-11, Vol.124, p.110974-110974, Article 110974

Ort / Verlag

Elsevier B.V

Erscheinungsjahr

2023

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• •IL-7 as a key component in inducing T cell activation, proliferation and cytotoxic activity.•our study demonstrate that IL-7 could promote proliferation of anti-CD19 CAR-T cells and increase the ratio of CD4 + CAR + population to possessed stronger the tumoricidal effect in vivo study.•IL-7 enhanced DNA synthesis in S phase and modulating cell cycle regulatory proteins.•Additionally, our study shows that IL-7 affected the expression of CDKN1A in CAR-T cells through miRNA-98-5p. CAR-T targeting CD19 have achieved significant effects in the treatment of B-line leukemia and lymphoma. However, the treated patients frequently relapsed and could not achieve complete remission. Therefore, improving the proliferation and cytotoxicity of CAR-T cells, reducing exhaustion and enhancing infiltration capacity are still issues to be solved. The IL-7 has been shown to enhance the memory characteristics of CAR-T cells, but the specific mechanism has yet to be elaborated. miRNAs play an important role in T cell activity. However, whether miRNA is involved in the activation of CAR-T cells by IL-7 has not yet been reported. Our previous study had established the 3rd generation CAR-T cells. The present study further found that IL-7 significantly increased the proliferation of anti-CD19 CAR-T cells, the ratio of CD4 + CAR + cells and the S phase of cell cycle. In vivo study NAMALWA xenograft model showed that IL-7-stimulated CAR-T cells possessed stronger tumoricidal efficiency. Further we validated that IL-7 induced CAR-T cells had low expression of CDKN1A and high expression of miRNA-98-5p. Additionally, CDKN1A was associated with miRNA-98-5p. Our results, for the first time, suggested IL-7 could conspicuously enhance the proliferation of CAR-T cells through miRNA-98-5p targeting CDKN1A expression, which should be applied to CAR-T production.