PD1 is transcriptionally regulated by LEF1 in mature T cells

Zhao，Pin1; Sun，Lanming2; Zhao，Cong2; Malik，Samiullah3

2023-09-01

10.1016/j.imbio.2023.152708

Immunobiology   影响因子和分区

0171-2985

1878-3279

The role of programmed cell death 1 (PD1) in cancer immune evasion is of considerable importance, prompting the development of monoclonal antibodies that specifically target PD-1 to enhance the immune system for cancer therapy. Nevertheless, the efficacy of PD1/programmed cell death-Ligand 1 (PD-L1) blocking antibodies is limited to certain patients or tumor types. Although researchers have demonstrated the influence of PD-1 on the positive selection of T cells, its effect on the T-cell repertoire remains uncertain. Lymphoid enhancer binding factor 1 (LEF1) has been known to play a critical role as a transcription factor in the development and maturation of T cells. Despite the greater focus on the study of its homologous protein, T cell factor 1 (TCF1), we discovered that LEF1 had a positive regulatory effect on the transcription of PD1 in mature T cells, including CD4+ T cells, CD8+ T cells, and Treg cells. This finding was observed in LEF1 knockout and LEF1-stimulated mice models. Additionally, we confirmed the direct regulation of PD1 by LEF1 in tumor-infiltrating lymphocytes through tumor-implantation experiments. The direct regulation of PD1 by LEF1 was further validated in the LEF1 knockout cell line. The results of our study provide novel perspectives on the regulation of PD1 in immune responses and investigate potential approaches for clinical anti-PD1 therapy.

CD8+ T cells Concanavalin A LEF1 PD1 Treg cells

SCI

英语

第一 ; 通讯

Basic and Applied Basic Research Foundation of Guangdong Province[2020A1515110742];

Immunology

Immunology

WOS:001050166800001

ELSEVIER GMBH

IMMUNOLOGY

2-s2.0-85166264729

Scopus

1.National Clinical Research Center for Infectious Diseases,The Third People's Hospital of Shenzhen,Southern University of Science and Technology,Shenzhen,China
2.Department of Prevention,Health Care and Fertility,Xinfuli Community Hospital,Beijing,Linhongnong Road, Dahongmen, Fengtai District,China
3.Department of Pathogen Biology,Shenzhen University Health Science Center,Shenzhen,518055,China

Zhao，Pin,Sun，Lanming,Zhao，Cong,et al. PD1 is transcriptionally regulated by LEF1 in mature T cells[J]. Immunobiology,2023,228(5).

Zhao，Pin,Sun，Lanming,Zhao，Cong,&Malik，Samiullah.(2023).PD1 is transcriptionally regulated by LEF1 in mature T cells.Immunobiology,228(5).

Zhao，Pin,et al."PD1 is transcriptionally regulated by LEF1 in mature T cells".Immunobiology 228.5(2023).