Banca de QUALIFICAÇÃO: NATALIA LUIZA DE LIMA MARIANO

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : NATALIA LUIZA DE LIMA MARIANO
DATE: 16/10/2025
TIME: 09:30
LOCAL: videoconferência.
TITLE:

Evaluation of immunosuppression in the tumor microenvironment of colorectal cancer after treatment with a nanosystem containing curcumin and a toll-like receptor 7 and 8 agonist (R848)

KEY WORDS:

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

PAGES: 81
BIG AREA: Ciências Biológicas
AREA: Morfologia
SUMMARY:

Colorectal cancer (CRC) is a disease that leads to a high annual mortality rate worldwide and is a major public health challenge. New treatment options, particularly in the area of immunotherapy, need to be developed. The objective of this research was to analyze the immunological profile of the Tumor Microenvironment (TME) via dendritic cells and M2 macrophages after treatment with Carboxymethylated Cashew Gum (GCCM) nanoparticles containing Toll-like receptor 7 and 8 agonist (R848) and curcumin in colorectal cancer. For this purpose, the allograft primary colorectal cancer model in Balb/C mice was used, with the inoculation of 1 x 106 CT-26 cells into the right flank of the mice. The animals in the experimental groups: GCCM+CURC, GCCM+R848, GCCM+CURC+R848, GCCM+CURC+PTX and SALINA were euthanized on the 21st day after being subjected to three treatments every 5 days, with tumors, inguinal lymph nodes and blood removed for molecular and cellular studies related to immunosuppression through immunohistochemistry, rt-PCR and blood count techniques. The results showed that the GCCM+CURC+R848 and GCCM+CURC+PTX nanoformulations presented an antitumor potential by downregulating immunosuppression, increasing the inflammatory infiltrate both by blood lymphocytosis (both p<0.0001) and in the TMA (p<0.0001 and p<0.01), respectively. In MAT, there was a reduction in the expression of CD163 (both, p<0.0001) and CD25 (GCCM+CURC+PTX, p<0.001), as well as an increase in the expression of CD8 (GCCM+CURC+R848, p<0.05) when compared to animals in the saline group. Furthermore, there was a decrease in the gene expression of the TL2 agonist in all experimental groups (All, p<0.0001). Therefore, it is possible to conclude that the tested nanoformulations, mainly GCCM+CURC+R848, were able 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 the lymph nodes, which is often associated with pro-tumor responses. In this context, these results demonstrate a great therapeutic and innovative potential of immunotherapy for colorectal cancer.

COMMITTEE MEMBERS:
Interno - 1667882 - BENTO JOAO DA GRACA AZEVEDO ABREU
Interna - 2477216 - NAISANDRA BEZERRA DA SILVA FARIAS
Presidente - 2329140 - RAIMUNDO FERNANDES DE ARAUJO JUNIOR
Interna - 1733434 - RENATA FIGUEIREDO ANOMAL