PD1 is transcriptionally regulated by LEF1 in mature T cells

Abstract

Programmed cell death 1 (PD1) plays a vital role in cancer immune evasion. So monoclonal antibodies targeting PD-1 to boost the immune system are being developed for the treatment of cancer. But the effect of PD1/PD-L1 blocking antibody only works in a subset of patients or some tumors. It is well established that PD-1 can affect the positive selection of T cells. Mice lacking PD1 or PD-L1 had more DP T cells in the thymus. However, how it affects the T-cell repertoire is not very clear. For T cell development and maturation, TCF1 and its homolog LEF1, act as indispensable factors and TCF1 has been most studied. In our work, we found that LEF1, not TCF1, positively regulated the transcription of PD1 by generating two mice models, including ERT2-CRE-LEF1flox/flox mice and concanavalin A (ConA)-mediated T activation mice model. We investigated LEF1 and PD1 expression in mature T cells, including CD4+ T cells, CD8+ T cells, and Treg cells in these two mice models. And we also evaluated the expression of PD1 in tumor-infiltrating lymphocytes in the tumor-implantation experiments. Furthermore, the regulation of PD1 by LEF1 was verified in LEF1 knockdown cells. Our conclusions provided a novel insight into PD1 regulation in immune responses and explored potential strategies for clinical anti-PD1 treatment.