2. Academic Validation
  3. Poliovirus receptor (PVR) mediates carboplatin-induced PD-L1 expression in non-small-cell lung cancer cells

Poliovirus receptor (PVR) mediates carboplatin-induced PD-L1 expression in non-small-cell lung cancer cells

  • Biochim Biophys Acta Gen Subj. 2023 Jul 27;130439. doi: 10.1016/j.bbagen.2023.130439.
Chen Fu 1,  Zongcai Liu 2,  Taixue An 3,  Haixia Li 3,  Xiumei Hu 3,  Xin Li 3,  Xinyao Liu 3,  Danjuan Wu 3,  Ruyi Zhang 3,  Kui Li 4,  Yurong Qiu 5,  Haifang Wang 6
Affiliations

Affiliations

  • 1 Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Department of Clinical Laboratory, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510655, China.
  • 2 The Laboratory of Endocrinology and Metabolism, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China.
  • 3 Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • 4 Guangzhou Huayinkang Medical Laboratory Center Co., Ltd., Guangzhou 510515, China. Electronic address: likui1211@163.com.
  • 5 Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Guangzhou Huayinkang Medical Laboratory Center Co., Ltd., Guangzhou 510515, China. Electronic address: qyr@smu.edu.cn.
  • 6 Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: wanghaifang@smu.edu.cn.
PMID: 37516256 DOI: 10.1016/j.bbagen.2023.130439
Abstract

Programmed death-ligand-1 (PD-L1) is an immune suppressor that inhibits T cell based immunity. Anti-PD-L1/PD-1 immunotherapy benefits those patients receiving platinum-based combinational chemotherapy. However, the underlying mechanism is still largely unknown. In this study, we found that carboplatin could induce PD-L1 expression in NSCLC H292, A549 and H1299 cells in a dose-dependent manner. mRNA Sequencing and the subsequent validation assays found that carboplatin significantly induced PVR expression, which is considered as an immuno-adhesion molecule. Mechanistically, PVR knockdown significantly abrogated carboplatin-induced PD-L1 expression. Functionally, knockdown of PVR significantly reversed the CD3+ T cells proliferation inhibition caused by carboplatin increased PD-L1. Moreover, the carboplatin-induced PVR and subsequent up-regulation of PD-L1 might be mediated via the EGFR, PI3K/Akt, and ERK signaling pathways. Immunohistochemical staining results showed that the PD-L1 expression was positively associated with PVR expression in clinical NSCLC samples. Our study reveals a novel regulatory mechanism of PD-L1 expression, provides evidence that carboplatin inhibits tumor immune response by up-regulating PD-L1 expression and explains the rationale for combining platinum-based chemotherapy with PD-L1/PD-1 inhibitors.

Keywords

Carboplatin; NSCLC; PD-L1; PVR.

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