Banca de QUALIFICAÇÃO: SHIRLEY VITORIA DE PAIVA SOUZA

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : SHIRLEY VITORIA DE PAIVA SOUZA
DATE: 08/05/2025
TIME: 14:00
LOCAL: REMOTA - https://meet.google.com/jfm-iqgz-cnh
TITLE:

M1 MACROPHAGE EXTRACELLULAR VESICLES AND TLR3 AGONIST NANOPARTICLES DOWN-REGULATE IMMUNOSUPPRESSION AND METASTASIS VIA AKT/TAM IN TRIPLE-NEGATIVE BREAST CANCER

KEY WORDS:

Exosomes; immunotherapy; nanomedicine; TLR agonists; targeted immune response.

PAGES: 26
BIG AREA: Ciências da Saúde
AREA: Farmácia
SUMMARY:

Metastasis induced by tumor immune escape has been implicated as one of the factors for the aggressiveness of Triple-negative breast cancer. Macrophage type 1-derived extracellular vesicles (M1EVs) were isolated and associated with PLGA nanoparticles loaded with the TLR3 agonist poly I:C (NPIC) as a therapeutic association strategy to investigate its anti-tumoral activity by down-regulating the tumor immune escape in the TME of breast cancer in a mouse model of orthotopic tumor growth. Tumors were evaluated by qRT-PCR and immunohistochemistry. Cell uptake and polarization of murine macrophages (RAW 264.7 cells) were analyzed in vitro by immunofluorescence and flow cytometer, respectively. Furthermore, mice survival, lymph nodes, and metastasis also were evaluated. In the animal model, the combination therapy down-regulated the tumorigenic course by TME immunomodulation, leading to reduction of primary tumor size (p < 0.0001) and metastasis with a mice’s survival extension for 11 days. Importantly, it was observed that the innate and adaptive immune responses improved, as indicated by an increase of the CD8 expression (p < 0.0001) and a reduction of PD-L1in the TME, as well as, an increase of CD11c expression in lymph node (p < 0.0001). Likewise, the combination therapy negatively modulated the tumor progression by reducing the expression of AKT1 (p < 0.001) and increasing the E-cadherin one (p < 0.01). Based on these results, the combination therapy worked as a “vaccine” provoking an immunomodulation in the TME and down-regulating the metastasis in a murine model of triple-negative breast cancer.

COMMITTEE MEMBERS:
Externa ao Programa - 2477216 - NAISANDRA BEZERRA DA SILVA FARIAS - nullPresidente - 2329140 - RAIMUNDO FERNANDES DE ARAUJO JUNIOR
Externa ao Programa - 1733434 - RENATA FIGUEIREDO ANOMAL - null