APLNR inhibited nasopharyngeal carcinoma growth and immune escape by downregulating PD-L1 PMID: 38909500

ADC Targets in Oncology

2026-04-10

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

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: [email protected].

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.