1. Academic Validation
  2. APLNR inhibited nasopharyngeal carcinoma growth and immune escape by downregulating PD-L1

APLNR inhibited nasopharyngeal carcinoma growth and immune escape by downregulating PD-L1

  • Int Immunopharmacol. 2024 Aug 20:137:112523. doi: 10.1016/j.intimp.2024.112523.
Ying Liu 1 Nan Li 1 Yilin Guo 1 Qing Zhou 2 Yuqin Yang 3 Jiaxue Lu 1 Ziying Tian 1 Jieyu Zhou 1 Shiqi Yan 1 Xiayu Li 4 Lei Shi 5 Su Jiang 1 Junshang Ge 6 Ranran Feng 7 Donghai Huang 8 Zhaoyang Zeng 6 Songqing Fan 5 Wei Xiong 6 Guiyuan Li 6 Wenling Zhang 9
Affiliations

Affiliations

  • 1 Department of Medical Laboratory Science, the Third Xiangya Hospital, Central South University, Changsha, Hunan, China; Department of Medical Laboratory Science, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
  • 2 Department of Clinical Laboratory, First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China.
  • 3 Shenzhen Maternity &Child Healthcare Hospital Clinical Laboratory, Shenzhen, Guangdong, China.
  • 4 Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, the Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • 5 Department of Pathology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • 6 NHC Key Laboratory of Carcinogenesis, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China; The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medicine Sciences, Central South University, Changsha, Hunan, China.
  • 7 Department of Andrology, Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan, China.
  • 8 Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • 9 Department of Medical Laboratory Science, the Third Xiangya Hospital, Central South University, Changsha, Hunan, China; Department of Medical Laboratory Science, Xiangya School of Medicine, Central South University, Changsha, Hunan, China. Electronic address: zhangwenling@csu.edu.cn.
Abstract

Background: APLNR is a G protein-coupled receptor and our previous study had revealed that APLNR could inhibit nasopharyngeal carcinoma (NPC) growth and metastasis. However, the role of APLNR in regulating PD-L1 expression and immune escape in NPC is unknown.

Methods: We analyzed the expression and correlation of APLNR and PD-L1 in NPC tissues and cells. We investigated the effect of APLNR on PD-L1 expression and the underlying mechanism in vitro and in vivo. We also evaluated the therapeutic potential of targeting APLNR in combination with PD-L1 antibody in a nude mouse xenograft model.

Results: We found that APLNR was negatively correlated with PD-L1 in NPC tissues and cells. APLNR could inhibit PD-L1 expression by binding to the FERM domain of JAK1 and blocking the interaction between JAK1 and IFNGR1, thus suppressing IFN-γ-mediated activation of the JAK1/STAT1 pathway. APLNR could also inhibit NPC immune escape by enhancing IFN-γ secretion and CD8+ T-cell infiltration and reducing CD8+ T-cell Apoptosis and dysfunction. Moreover, the best effect was achieved in inhibiting NPC growth in nude mice when APLNR combined with PD-L1 antibody.

Conclusions: Our study revealed a novel mechanism of APLNR regulating PD-L1 expression and immune escape in NPC and suggested that APLNR maybe a potential therapeutic target for NPC immunotherapy.

Keywords

APLNR; IFN-γ; Immune Escape; Nasopharyngeal Carcinoma; PD-L1.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-16997
    99.97%, JAK1 抑制剂
    JAK