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Research progress on the intrinsic non-immune function of PD-L1 in tumors (Review)
Jiao Deng1, Wei Jiang1, Liang Liu1
1Gastrointestinal Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Abstract:
Programmed death ligand 1 (PD-L1) is widely expressed in human tumors. It is widely known for its immunosuppressive function as it can help tumor cells evade T cell immune killing through the PD-1/PD-L1 signal. A number of clinical trials have proved that the destruction of the combination of PD-1 and PD-L1 by antibodies could significantly affect patients with advanced cancer. However, a number of patients with cancer still cannot benefit from PD-1/PD-L1 blocking therapy. The main reason is that PD-L1 also has some intrinsic regulatory functions to promote the progression of tumors. PD-L1 Protein contains an intrinsic domain that could link to other signal pathways, but the mechanism has not yet been fully revealed. The present review mainly discussed the non-immune checkpoint functions of PD-L1, such as its role in regulating cell proliferation, cell metabolism, drug resistance and maintaining epithelial-mesenchymal transition and stemness.
Insights
Programmed death ligand 1 (PD-L1) has immune checkpoint functions and also promotes tumor progression. Understanding PD-L1's non-immune roles is crucial for improving cancer therapies beyond current blocking strategies.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Programmed death ligand 1 (PD-L1) is expressed in human tumors and mediates immune suppression via the PD-1/PD-L1 pathway.
- Antibody-mediated blockade of PD-1/PD-L1 shows efficacy in advanced cancer but benefits a subset of patients.
- Tumor cells may evade therapy due to PD-L1's intrinsic, non-immune functions promoting tumor progression.
Purpose of the Study:
- To review the non-immune checkpoint functions of PD-L1 in cancer.
- To elucidate the mechanisms by which PD-L1 promotes tumor progression independent of immune signaling.
- To highlight potential therapeutic strategies targeting PD-L1's intrinsic roles.
Main Methods:
- Literature review of studies investigating PD-L1's functions beyond immune checkpoint inhibition.
- Analysis of research on PD-L1's interactions with intracellular signaling pathways.
- Synthesis of findings related to PD-L1's impact on cell proliferation, metabolism, and drug resistance.
Main Results:
- PD-L1 possesses intrinsic domains that interact with signaling pathways, influencing tumor biology.
- PD-L1 regulates key cellular processes including proliferation, metabolism, and epithelial-mesenchymal transition (EMT).
- PD-L1 contributes to maintaining cancer stemness and acquired drug resistance.
Conclusions:
- PD-L1's multifaceted roles extend beyond immune evasion, impacting tumor growth and survival.
- Targeting PD-L1's intrinsic functions may overcome resistance to current PD-1/PD-L1 therapies.
- Further research into PD-L1's non-immune mechanisms is essential for developing novel cancer treatments.
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