Banca de DEFESA: Camila Magalhães Cardador

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : Camila Magalhães Cardador
DATE: 20/06/2023
TIME: 14:00
LOCAL: Auditório 3
TITLE:

DOXORUBICIN-INDUCED IMMUNOGENIC CELL DEATH IS ABLE TO IMPAIR TUMOR PROGRESSION AND DISTANT METASTASIS IN A HIGHLY AGGRESSIVE BREAST CANCER TUMOR MODEL

KEY WORDS:

breast cancer; doxorubicin; vaccine; immunogenic cell death.

PAGES: 45
BIG AREA: Ciências Biológicas
AREA: Biologia Geral
SUMMARY:

Cancer is an individual disease, and its formation and development are specific to each host. Conventional treatments are ineffective in complex cases such as metastases and have serious adverse effects. New strategies are needed to approach the problem, and the use of Immunogenic Cell Death as an initiator of the immune system response through the exposure of damage-associated molecular patterns (DAMPs) by cancer cells is presented as a personalized therapeutic vaccination approach in this work. To this purpose, murine mammary adenocarcinoma cells were exposed to doxorubicin in order to induce the release of markers associated with immunogenic cell death, such as ATP and calreticulin, and grafted subcutaneously in BALB/c mice. As a protocol control, cells were also exposed to death by necrosis. This protocol, here called “vaccination”, was performed three times, with an interval of seven days between each repetition. After the last transplantation of cells in the stage of immunogenic death, the vaccination protocol was challenged with subcutaneous grafting of the same unexposed cancer cells, without exposure to doxorubicin, on the flank opposite that of vaccination. The “challenge” stage assesses whether or not mice have a specific immune response to the cancer cells. The clinical follow-up of the mice was carried out for 6 weeks, during which the mice were scanned to assess the appearance of pulmonary metastases and had their tumor appearance and volume monitored. Flow cytometry and image analysis evaluated the induction of doxorubicin-initiated immunogenic cell death in murine mammary adenocarcinoma cells. The results showed that mice vaccinated with cells in the immunogenic cell death stage after exposure to doxorubicin did not present a primary tumor during the 6 weeks of evaluation, as well as there were no indications of the development of metastatic lesions in secondary sites.

BANKING MEMBERS:
Presidente - 1929494 - JOAO PAULO FIGUEIRO LONGO
Externa ao Programa - 2862542 - KELLY GRACE MAGALHAES
Externa à Instituição - MARTHA DE SOUZA TEIXEIRA ROCHA - ONCOVIDAVET
Externo à Instituição - MOSAR CORREA RODRIGUES - STRI