Dataset Information

Nuclear PD-L1 promotes EGR1-mediated angiogenesis and accelerates tumorigenesis.

ABSTRACT: Targeting programmed cell death protein ligand 1 (PD-L1) remains one of the most essential immunotherapies in cancer^1,2. PD-L1 has been detected in the nucleus in multiple malignancies, playing an oncogenic role independent of immune checkpoint regulation^3-5. Howbeit, the regulatory function of nuclear PD-L1 (nPD-L1) remains to be fully understood. Here, we report that nPD-L1 is an endogenous accelerator for cancer angiogenesis. First, we found that an abundant proportion of PD-L1 was distributed within the nucleus of uveal melanoma samples, which is associated with an unfavorable outcome. Moreover, the capacity of promoting angiogenesis was largely attenuated in the nPD-L1-deficient cells both in vivo and in vitro. Mechanistically, nPD-L1 facilitates p-STAT3 binding to the promoter of early growth response-1 (EGR1), resulting in the activation of EGR1-mediated angiogenesis. Therapeutically, the inhibition of histone deacetylase 2 restores the normal acetylation level of PD-L1, blocking its nuclear translocation and thereby attenuating tumor angiogenesis. Conclusively, we reveal that nPD-L1 promotes angiogenesis in malignancies, and provide a novel anti-vascularization strategy through blocking aberrant PD-L1 nuclear translocation for tumor therapy.

SUBMITTER: Yu J

PROVIDER: S-EPMC10050073 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Nuclear PD-L1 promotes EGR1-mediated angiogenesis and accelerates tumorigenesis.

Yu Jie J Zhuang Ai A Gu Xiang X Hua Yu Y Yang Ludi L Ge Shengfang S Ruan Jing J Chai Peiwei P Jia Renbing R Fan Xianqun X

Cell discovery 20230328 1

Targeting programmed cell death protein ligand 1 (PD-L1) remains one of the most essential immunotherapies in cancer<sup>1,2</sup>. PD-L1 has been detected in the nucleus in multiple malignancies, playing an oncogenic role independent of immune checkpoint regulation<sup>3-5</sup>. Howbeit, the regulatory function of nuclear PD-L1 (nPD-L1) remains to be fully understood. Here, we report that nPD-L1 is an endogenous accelerator for cancer angiogenesis. First, we found that an abundant proportion o ...[more]

PMID: 36977660

Similar Datasets

Project description:Chronic exposure to environmental arsenic promotes lung cancer. Emerging evidence indicates that compromised host immunity, particularly T cell anti-tumor immunity, may play a critical role in cancer development. However, there is a knowledge gap in terms of the effects of arsenic exposure on T cell anti-tumor immunity and how that may contribute to arsenic lung carcinogenicity. Immunosuppression has been known as a risk factor for many types of cancer, including lung cancer. The development of cancer indicates the success of immunosuppression and escape of cancer cells from host anti-tumor immunity in which T cells are the major component. The anti-tumor immunity is mainly executed by CD8 cytotoxic T cells through their anti-tumor effector function, which can be regulated by immune checkpoint pathways. Some inhibitory receptors on the T cell membrane and their ligands form these pathways, among which programmed death-1 (PD-1), a T cell inhibitory receptor, and its ligand, programmed death-ligand 1 (PD-L1), are best characterized. A/J mice are naturally sensitive to pulmonary carcinogens, prone to develop spontaneous lung tumors later in life and have been frequently used as an animal model for lung tumorigenesis research. Chronic arsenic administration through drinking water has been shown to enhance tumor formation in the lungs of A/J mice. In the current study, using this mouse model we want to determine whether PD-1/PD-L1 plays a role in arsenic-enhanced lung tumorigenesis. The results showed that prolonged arsenic exposure up-regulated PD-1/PD-L1, increased regulatory T cells (Tregs), decreased CD8/Treg ratio, inhibited T cell antitumor function in the lungs and enhanced lung tumor formation, while inhibition of PD-1/PD-L1 restored CD8/Treg ratio and T cell anti-tumor effector function, and mitigated arsenic-enhanced lung tumorigenesis. In addition, inhibition of PD-1/PD-L1 could be a potential preventive strategy to mitigate the tumorigenic action of chronic arsenic exposure.

Dataset Information

Nuclear PD-L1 promotes EGR1-mediated angiogenesis and accelerates tumorigenesis.

Publications

Nuclear PD-L1 promotes EGR1-mediated angiogenesis and accelerates tumorigenesis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets