Banca de DEFESA: GEORGE ALEXANDRE LIRA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : GEORGE ALEXANDRE LIRA
DATE: 11/12/2025
TIME: 08:00
LOCAL: REMOTA
TITLE:

IMPACT OF TUMOR-ASSOCIATED MACROPHAGES AND STAT3/NF-ΚB SIGNALING PATHWAY ACTIVATION ON IMMUNOSUPPRESSION AND CERVICAL CANCER PROGRESSION: AN INTEGRATED RETROSPECTIVE AND PROSPECTIVE APPROACH IN PATIENTS FROM THE LIGA NORTE-RIOGRANDENSE CONTRA O CÂNCER, NATAL- RN, BRAZIL

KEY WORDS:

M2-TAM; STAT3; Cervical cancer; Recurrence; Overall survival; Tumor progression; Immunotherapy; Cytokines; Immune response.

PAGES: 152
BIG AREA: Ciências da Saúde
AREA: Enfermagem
SUMMARY:

This study explored the interaction between tumor-associated macrophages (TAMs), immunoregulatory pathways, and clinical outcomes in cervical carcinoma (CC) through two complementary cohorts comprising a total of 791 patients. In a retrospective analysis of 691 cases, TAM infiltration and activation of the STAT3/NF-κB signaling pathway were assessed using tissue microarrays (TMA) and immunohistochemistry. A high stromal density of CD163⁺/CD204⁺ TAMs was significantly associated with increased expression of E-cadherin, Vimentin, MMP9, VEGF-α, Bcl-2, Ki-67, CD25, MIF, FOXP3, and IL-17 (all p < 0.0001). Advanced stage IV disease (TNM) showed a strong correlation with STAT3/NF-κB, CD25, VEGF-α, MIF, and Ki-67 expression (all p < 0.001). Survival analysis revealed that elevated levels of SNAIL, E-cadherin, and Ki-67 were independent predictors of poor overall and recurrence-free survival (HR = 1.52, 1.78, and 1.44, respectively). In a complementary prospective study involving 100 colorectal cancer patients followed from 2018 to 2023, tumor and blood samples were analyzed by qRT-PCR, immunohistochemistry, and flow cytometry. The results demonstrated that M2-polarized TAM infiltration, mediated by STAT3/NF-κB activation, correlated with increased expression of Ki-67, VEGF-α, and FOXP3 (p < 0.001). Furthermore, deletion of the FOXP3 T allele, HLA-G polymorphisms, and activation of the CXCL12-CXCR4 axis were associated with elevated STAT3 and SNAIL expression and higher circulating levels of IL-4, IL-6, IL-12, and IL-17, leading to increased mortality risk. Across both studies, these findings indicate that M2-type TAM infiltration and activation of the STAT3/NF-κB and CXCL12-CXCR4 pathways drive tumor progression and systemic immunosuppression— including FOXP3 polymorphisms in regulatory T cells and dysregulation of antitumor cytokines—ultimately contributing to unfavorable clinical outcomes in cervical carcinoma. The integration of retrospective and prospective data underscores the central role of TAM-mediated immune modulation as a prognostic and potentially therapeutic target in cervical cancer.

COMMITTEE MEMBERS:
Interna - 2323511 - ADRIANA AUGUSTO DE REZENDE
Externo ao Programa - 1667882 - BENTO JOAO DA GRACA AZEVEDO ABREU - nullExterna à Instituição - KARUZA MARIA ALVES PEREIRA - UFC
Externo à Instituição - RADAN ELVIS MATIAS DE OLIVEIRA - UFERSA
Presidente - 2329140 - RAIMUNDO FERNANDES DE ARAUJO JUNIOR