PD-L1/p-STAT3 promotes the progression of NSCLC cells by regulating TAM polarization
Rui Zhang1,2, Ziqi Meng1,2, Xuwei Wu1,2
1Department of Pathology and Cancer Research Center, Yanbian University Medical College, Yanji, China.
Abstract:
PD-L1 is closely related to the immune escape process of tumour cells, and targeted PD-L1 clinical immunotherapy has been implemented. However, whether PD-L1 is involved in TAM/M2 polarization in the TME of NSCLC and its specific mechanism remain unclear. In order to clarify the specific role of PD-L1 in NSCLC and to seek new treatments for NSCLC, we designed a series of experimental studies. After constructing the co-culture system and conditioned medium system, the proliferation, apoptosis, metastasis, angiogenesis, EMT process and stemness of NSCLC were detected by MTT, flow cytometry, Transwell, endothelial cell tube formation and western blot assays. The results showed that αPD-L1 reversed TAM/M2 polarization by suppressing STAT3 phosphorylation in TAM/M2, therapy inhibiting NSCLC cell migration, angiogenesis, EMT process and stemness. However, αPD-L1 had no effect on the proliferation and apoptosis abilities of NSCLC cells. In vivo experiments showed that αPD-L1 inhibited lung metastasis of NSCLC and reversed TAM/M2 polarization in TME. The study investigates the mechanism by which PD-L1 regulates TAMs polarization in TME and promotes malignant progression of NSCLC, providing a new theoretical basis for PD-L1 targeted therapy of NSCLC.
Insights
Targeting PD-L1 (programmed death-ligand 1) with αPD-L1 therapy reverses tumor-promoting M2 macrophage polarization in non-small cell lung cancer (NSCLC). This approach inhibits NSCLC metastasis and progression, offering new therapeutic strategies.
Area of Science:
- Immunology
- Oncology
- Cancer Biology
Background:
- Programmed death-ligand 1 (PD-L1) is crucial for tumor immune escape and targeted therapies are in clinical use.
- The role and mechanism of PD-L1 in regulating tumor-associated macrophage (TAM) M2 polarization within the tumor microenvironment (TME) of non-small cell lung cancer (NSCLC) remain largely unknown.
Purpose of the Study:
- To elucidate the specific function of PD-L1 in NSCLC progression.
- To investigate the mechanism of PD-L1 in TAM/M2 polarization.
- To explore novel therapeutic strategies for NSCLC targeting PD-L1.
Main Methods:
- Co-culture and conditioned medium systems were established to study NSCLC.
- In vitro assays included MTT, flow cytometry, Transwell, endothelial cell tube formation, and western blot to assess NSCLC cell behavior.
- In vivo experiments evaluated the effects of αPD-L1 on lung metastasis and TME polarization.
Main Results:
- αPD-L1 treatment reversed TAM/M2 polarization by inhibiting STAT3 phosphorylation in TAMs/M2.
- αPD-L1 therapy suppressed NSCLC cell migration, angiogenesis, epithelial-mesenchymal transition (EMT), and stemness.
- αPD-L1 did not significantly affect NSCLC cell proliferation or apoptosis.
- In vivo studies confirmed that αPD-L1 inhibited lung metastasis and reversed TAM/M2 polarization in the TME.
Conclusions:
- PD-L1 plays a significant role in promoting NSCLC malignant progression by regulating TAM/M2 polarization in the TME.
- αPD-L1 therapy effectively inhibits NSCLC metastasis and progression by targeting PD-L1-mediated TAM/M2 polarization.
- This research provides a new theoretical foundation for PD-L1 targeted immunotherapy in NSCLC treatment.
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