2. Academic Validation
  3. Loss of RPN1 Promotes Antitumor Immunity via PD-L1 Checkpoint Blockade in Triple-negative Breast Cancer--Experimental Studies

Loss of RPN1 Promotes Antitumor Immunity via PD-L1 Checkpoint Blockade in Triple-negative Breast Cancer--Experimental Studies

  • Int J Surg. 2024 Dec 20. doi: 10.1097/JS9.0000000000002164.
Mengxue Wang 1 2,  Xunjia Li 3 4,  Yushen Wu 2 5,  Long Wang 2 6,  Xue Zhang 2,  Meng Dai 7,  Yang Long 8,  Deyu Zuo 4 9,  Shengwei Li 10,  Xuedong Yin 11
Affiliations

Affiliations

  • 1 Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 2 Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 3 Department of Nephrology, Chongqing Traditional Chinese Medicine Hospital, Chongqing, China.
  • 4 Chongqing precision medical industry technology research institute, Chongqing, China.
  • 5 Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 6 Department of Breast Cancer Center, Chongqing University Cancer Hospital, Chongqing, China.
  • 7 Department of Oncology, Chongqing Traditional Chinese Medicine Hospital, Chongqing, China.
  • 8 Division of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 9 Department of Rehabilitation Medicine, Chongqing Traditional Chinese Medicine Hospital, Chongqing, China.
  • 10 Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 11 Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
PMID: 39705151 DOI: 10.1097/JS9.0000000000002164
Abstract

Background: RPN1, also known as ribophorin I (RPN1), is a type I transmembrane protein that plays an important role in glycosylation. However, the effects of RPN1 on Cancer progression and immune evasion in breast Cancer (BC) have not been identified.

Materials and methods: The expression of RPN1 was evaluated using RT-qPCR and immunohistochemistry (IHC). The effects of RPN1 on tumor cells were assessed using RT-qPCR, western blotting, flow cytometry, Cell Counting Kit 8 (CCK-8), colony formation assays, and in vivo experiments. The mechanism by which RPN1 modifies programmed death ligand-1 (PD-L1) and the tumor microenvironment was examined by RT-qPCR, western blotting, co-immunoprecipitation (Co-IP), and flow cytometry. The influence of the transcription factor YY1 on RPN1 expression was revealed using bioinformatics analysis, RT-qPCR, and dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays.

Results: RPN1 is aberrantly expressed in triple-negative breast Cancer (TNBC) cells, correlating with increased proliferation and poor prognosis. RPN1 mediates the post-translational modification of PD-L1, enhancing its glycosylation and stability, thus facilitating PD-L1-mediated immune escape and tumor growth. The deletion of RPN1 improves the TNBC microenvironment and enhances the efficacy of anti-PD-1 therapy. Additionally, we uncovered a novel regulatory axis involving YY1/RPN1/YBX1 in PD-L1 regulation, affecting TNBC growth and metastasis.

Conclusions: Our preliminary study reveals that targeting RPN1 promotes immune suppression, providing a new potential immunotherapy strategy for TNBC. However, further research is necessary to fully elucidate and understand the specific mechanisms of RPN1 in TNBC and its potential for clinical application .

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