Study on the efficacy of IFN-γ- and sPD-1-overexpressing BMSCs in enhancing immune effects for the treatment of lung adenocarcinoma DOI Creative Commons

Yahui Xie,

Zhen Lv,

Y. W. Wang

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 13, 2025

Background Soluble programmed cell death receptor-1 (sPD-1) blocks the PD-1/PD-L1 pathway, reverses tumor immune suppression, and inhibits growth. However, clinical applications are limited by its poor tissue distribution rapid dispersion. Bone marrow-derived mesenchymal stem cells (BMSCs) favorable carriers for immunotherapy due to their capacity external gene introduction targeted homing. they may inadvertently promote Interferon-gamma (IFN-γ) BMSC-mediated growth stimulates antigen-presenting activate T lymphocytes. This study utilizes BMSCs transfected with IFN-γ as sPD-1, enabling homing of sPD-1 tissues, thereby enhancing efficacy sustained stability immunotherapy. Methods stable IFN-γ- sPD-1-overexpressing were successfully constructed lentiviral transfection. A non-contact co-culture system was established Lewis A549 lung adenocarcinoma observe changes in cancer after co-culture, using assays including migration invasion experiments, well cellular senescence detection. Additionally, a subcutaneous model C57BL/6J mice intervention studies. Tumor volume, apoptosis (assessed TUNEL assay), peripheral Treg (analyzed flow cytometry), histopathological markers (evaluated HE staining immunohistochemistry) analyzed. The expression levels BAX, BCL-2, AKT, PI3K, PD-L1 assessed quantitative PCR Western Blot. Results exhibited high bioactivity genetic stability, inhibiting proliferation, accelerating senescence, reducing invasion. Furthermore, upregulate Bax expression, downregulate Bcl-2, apoptosis. these alleviate inflammatory damage tumor-bearing mice, lower inhibit evasion, reduce PI3K/AKT PD-L1. Conclusion effectively progression. primary mechanisms include suppression growth, migration, invasion; promotion cells; modulation inhibition signaling pathway pathways.

Language: Английский

Study on the efficacy of IFN-γ- and sPD-1-overexpressing BMSCs in enhancing immune effects for the treatment of lung adenocarcinoma DOI Creative Commons

Yahui Xie,

Zhen Lv,

Y. W. Wang

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 13, 2025

Background Soluble programmed cell death receptor-1 (sPD-1) blocks the PD-1/PD-L1 pathway, reverses tumor immune suppression, and inhibits growth. However, clinical applications are limited by its poor tissue distribution rapid dispersion. Bone marrow-derived mesenchymal stem cells (BMSCs) favorable carriers for immunotherapy due to their capacity external gene introduction targeted homing. they may inadvertently promote Interferon-gamma (IFN-γ) BMSC-mediated growth stimulates antigen-presenting activate T lymphocytes. This study utilizes BMSCs transfected with IFN-γ as sPD-1, enabling homing of sPD-1 tissues, thereby enhancing efficacy sustained stability immunotherapy. Methods stable IFN-γ- sPD-1-overexpressing were successfully constructed lentiviral transfection. A non-contact co-culture system was established Lewis A549 lung adenocarcinoma observe changes in cancer after co-culture, using assays including migration invasion experiments, well cellular senescence detection. Additionally, a subcutaneous model C57BL/6J mice intervention studies. Tumor volume, apoptosis (assessed TUNEL assay), peripheral Treg (analyzed flow cytometry), histopathological markers (evaluated HE staining immunohistochemistry) analyzed. The expression levels BAX, BCL-2, AKT, PI3K, PD-L1 assessed quantitative PCR Western Blot. Results exhibited high bioactivity genetic stability, inhibiting proliferation, accelerating senescence, reducing invasion. Furthermore, upregulate Bax expression, downregulate Bcl-2, apoptosis. these alleviate inflammatory damage tumor-bearing mice, lower inhibit evasion, reduce PI3K/AKT PD-L1. Conclusion effectively progression. primary mechanisms include suppression growth, migration, invasion; promotion cells; modulation inhibition signaling pathway pathways.

Language: Английский

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