Banca de DEFESA: NATALIA LUIZA DE LIMA MARIANO

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : NATALIA LUIZA DE LIMA MARIANO
DATE: 04/12/2025
TIME: 08:30
LOCAL: videoconferência.
TITLE:

Evaluation of immunosuppression in colorectal cancer after treatment with a nanosystem using carboxymethylated cashew gum containing curcumin and an agonist of Toll-Like Receptors 7 and 8 (R848)

KEY WORDS:

Colorectal Neoplasm 1. Nanoparticles 2. Antineoplastic Agents 3. Animals 4.Immunotherapy 5.

PAGES: 96
BIG AREA: Ciências Biológicas
AREA: Morfologia
SUMMARY:

Colorectal cancer (CRC) is a disease that leads to a high mortality rate worldwide annually, representing a major public health challenge. In this context, new treatment alternatives, especially in the area of immunotherapy, need to be explored and developed. The objective of this research was to analyze the immunological profile of the Tumor Microenvironment (TMA) via dendritic cells and M2-type macrophages after colorectal cancer treatment with Carboxymethyl Cashew Gum (CCG) nanoparticles containing curcumin and an agonist of Toll-Like Receptors 7 and 8 (R848). For this, the primary-26 cell line cells into the right flank of the mice. The animals were separated into the following experimental groups: GCCM+CURC, GCCM+R848, GCCM+CURC+R848, GCCM+CURC+PTX, and SALINA, and were euthanized on the 21st day after undergoing measurements and three treatments every five days, respectively. At euthanasia, tumors, inguinal lymph nodes, and blood were collected for molecular and cellular studies related to immunosuppression using histopathology, immunohistochemistry, RT-PCR, and blood count techniques. The results showed that the nanoformulations present in GCCM+CURC+R848 and GCCM+CURC+PTX exhibited antitumor potential by generating the downregulation of immunosuppression, increasing the inflammatory infiltrate both by blood lymphocytosis (both, p<0.0001) and in the MAT (p<0.0001 and p<0.01), respectively. In the tumor microenvironment, there was a reduction in the expression of M2 macrophages and treg cells indicated by CD163 (both, p<0.0001) and CD25 (GCCM+CURC+PTX, p<0.001), as well as the presence of lymphocytes due to increased CD8 expression (GCCM+CURC+R848, p<0.05) when compared to animals in the SALINA group. Furthermore, there was a decrease in the gene expression of Toll-Like Receptor 2 (TLR2) in all experimental groups (All, p<0.0001). Therefore, it is possible to conclude that, of the nanoformulations tested, the GCCM+CURC+R848, in particular, managed to induce the downregulation of CD8 cell immune exhaustion in the tumor microenvironment by decreasing the infiltration of M2-TAM and Treg cells, as well as suppressing TLR2 in lymph nodes, which is associated with antitumor responses through dendritic cells and M1 macrophages. In this context, these results demonstrate that the use of a nanosystem made from carboxymethylated cashew gum containing curcumin associated with TLR 7 and 8 agonists may not only contain tumor progression but also block the immune evasion mechanism in the tumor microenvironment, making it less suppressive and more antitumor, representing a potentially innovative and effective therapeutic method for combating colorectal cancer.

COMMITTEE MEMBERS:
Externa à Instituição - ALEXIA NATHÁLIA BRÍGIDO ASSEF - UFC
Interno - 1667882 - BENTO JOAO DA GRACA AZEVEDO ABREU
Presidente - 2329140 - RAIMUNDO FERNANDES DE ARAUJO JUNIOR
Interna - 1733434 - RENATA FIGUEIREDO ANOMAL