Please use this identifier to cite or link to this item:
https://repositorio.ufrn.br/handle/123456789/49513| Title: | STAT3/NF‐κB signalling disruption in M2 tumour‐associated macrophages is a major target of PLGA nanocarriers/PD‐L1 antibody immunomodulatory therapy in breast cancer |
| Other Titles: | STAT3/NF‐κB signalling disruption in M2 tumour‐associated macrophages is a major target of PLGA nanocarriers/PD‐L1 antibody immunomodulatory therapy in breast cancer |
| Authors: | Cavalcante, Rômulo Ishikawa, Uta Silva, Emanuell Silva Jr, Arnóbio Araújo, Aurigena Cruz, Luis Chan, Alan Araújo Jr, Raimundo |
| Keywords: | Immunomodulation;M2‐like macrophages;NF‐κB;PD‐L1 antibody;PLGA nanoparticles;STAT3;tumour microenvironment |
| Issue Date: | 31-Mar-2021 |
| Publisher: | British journal of pharmacology |
| Citation: | Cavalcante, R. S., Ishikawa, U., Silva, E. S., Silva-Júnior, A. A., Araújo, A. A., Cruz, L. J., Chan, A. B., & de Araújo Júnior, R. F. STAT3/NF-κB signalling disruption in M2 tumour-associated macrophages is a major target of PLGA nanocarriers/PD-L1 antibody immunomodulatory therapy in breast cancer. Br J Pharmacol. 2021;178(11):2284-2304. doi:10.1111/bph.15373 |
| Portuguese Abstract: | Background and Purpose Inflammation associated with the tumour microenvironment (TME) is critical for cancer development, and immunotherapeutic strategies modulating the immune response in cancer have been crucial. In this study, a methotrexate‐loaded (MTX) poly(lactic‐co‐glycolic acid)‐based (PLGA) drug nanocarrier covered with polyethyleneimine (Pei) and hyaluronic acid (HA) was developed and combined with an PD‐L1 antibody to investigate anti‐cancer and immunomodulatory effects in breast cancer TME. Experimental Approach Naked or HA‐coated PeiPLGA‐MTX nanoparticles (NPs) were assessed on 4T1 breast cancer cells grown in culture and in a mouse model of orthotopic tumour growth. Tumours were evaluated by qRT‐PCR and immunohistochemistry. The cell death profile and cell migration were analysed in vitro in 4T1 cells. Polarization of murine macrophages (RAW cells) was also carried out. Key Results Naked or HA‐coated PeiPLGA‐MTX NPs used alone or combined with PD‐L1 antibody modified the tumourigenic course by TME immunomodulation, leading to reduction of primary tumour size and metastases. STAT3 and NF‐κB were the major genes downregulated by NPs. In tumor‐associated macrophages (TAM) such regulation switched M2 phenotype (CD163) towards M1 (CD68) and reduced levels of IL‐10, TGF‐β and CCL22. Moreover, malignant cells showed overexpression of FADD, APAF‐1, caspase‐3 and E‐cadherin, and decreased expression of Bcl‐2, MDR‐1, survivin, vimentin, CXCR4 and PD‐L1 after treatment with NPs. Conclusion and Implications NPs‐mediated STAT3/NF‐κB signalling axis suppression disrupted crosstalk between immune and malignant cells, reducing immunosuppression and critical pro‐tumour events. These findings provide a promising therapeutic approach capable of guiding the immune TME to suppress the development of breast cancer. |
| URI: | https://repositorio.ufrn.br/handle/123456789/49513 |
| Appears in Collections: | CB - DMOR - Artigos publicados em periódicos |
Files in This Item:
| File | Description | Size | Format | |
|---|---|---|---|---|
| BPH-178-2284.pdf | STAT3/NF-κB signalling disruption in M2 tumour-associated macrophages is a major target of PLGA nanocarriers/PD-L1 antibody immunomodulatory therapy in breast cancer | 116,43 MB | Adobe PDF | View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.