Banca de DEFESA: RÔMULO DOS SANTOS CAVALCANTE

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : RÔMULO DOS SANTOS CAVALCANTE
DATE: 02/10/2020
TIME: 08:00
LOCAL: DEFESA REMOTA - https://meet.google.com/mbk-esfc-qyh
TITLE:

IMMUNOMODULATION OF BREAST CANCER MICROENVIRONMENT BY HA-PEI-PLGA-MTX NANOPARTICLES COMBINED WITH ANTI-PD-L1 VIA SUPPRESSION OF IL-10/STAT3/NF-ΚB SIGNALING AXIS

KEY WORDS:

Immunomodulation, PLGA nanoparticles, Anti-PD-L1, STAT3, NF-κB, tumour microenvironment

PAGES: 47
BIG AREA: Ciências da Saúde
AREA: Farmácia
SUMMARY:

 

 

Inflammation associated with the tumour microenvironment (TME) in breast cancer is closely related to the development and progression of the tumour. In this sense understand the involved mechanisms, as well as ways to combat the inflammatory process is challenging and has been widely investigated. In this study, a novel immunotherapeutic approach using PLGA-based drug nanocarrier (methotrexate - MTX), covered with polyethyleneimine (Pei) and hyaluronic acid (HA), combined with anti-PD-L1 immune checkpoint inhibitor is suggested as way to reduce the development and progression of breast cancer through immunomodulating its tumour microenvironment. From the allographic model of orthotopic breast cancer development, the tumours were evaluated by qRT-PCR and immunohistochemistry. Complementary analysis of biocompatibility and internalization of nanoparticles, as well as the investigation of cell death profile, cells migration and polarization of macrophages were evaluated in vitro. Naked or HA-coated PeiPLGA-MTX nanoparticles, alone or combined with anti-PD-L1, promoted immunomodulation of the tumour microenvironment and consequent alteration in the tumorigenic course with significant reduction of the primary tumour and metastasis. In addition, the same treatments were able to considerably reduce the M2 macrophages population, as well as promoting downregulation of IL-10 / STAT3 / NF-κB signalling axis in the tumour microenvironment. The suppression of this signalling axis, especially in M2 macrophages, appears to have disrupted the crosstalk between immune and malignant cells, thus reducing critical pro-tumour events, such as: immune escape; cell survival; drug and apoptosis resistance, as well as some key mechanisms in the epithelial-mesenchymal transition. Such results shed light on the understanding of immunological mechanisms that underlie tumour progression and brings up a promising drug nanocarrier capable of satisfactorily modulating the immunological tumour microenvironment of breast cancer.

BANKING MEMBERS:
Interna - 2323511 - ADRIANA AUGUSTO DE REZENDE
Externa à Instituição - KARUZA MARIA ALVES PEREIRA - UFC
Externo ao Programa - 1752367 - PAULO MARCOS DA MATTA GUEDES
Presidente - 2329140 - RAIMUNDO FERNANDES DE ARAUJO JUNIOR
Externo à Instituição - RENATA FERREIRA DE CARVALHO LEITÃO - UFC