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High M2-TAM Infiltration and STAT3/NF-κB Signaling Pathway as a Predictive Factor for Tumor Progression and Death in

George Alexandre Lira1,2,3,4, Fábio Medeiros de Azevedo5, Ingrid Gabrielle Dos Santos Lins4

  • 1Cancer and Inflammation Research Laboratory, Department of Morphology, Federal University of Rio Grande do Norte Natal, Natal 59072-970, RN, Brazil.

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|July 27, 2024
PubMed
Summary

Tumor-associated macrophages (TAMs) and the STAT3/NF-κB pathway significantly impact cervical carcinoma (CC) progression. This research links M2-TAMs to poor prognosis and highlights their role in CC tumor advancement.

Keywords:
M2-TAMSTAT3cervical canceroverall survivalrecurrencetumor progression

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Area of Science:

  • Oncology
  • Immunology
  • Cell Biology

Background:

  • The tumor microenvironment (TME) is critical in cervical carcinoma (CC) progression, invasion, and metastasis.
  • Tumor-associated macrophages (TAMs) are key TME components, but their role in CC progression remains debated.
  • Understanding TAMs and associated signaling pathways is vital for CC prognosis.

Purpose of the Study:

  • To investigate the relationship between TAM infiltration and the STAT3/NF-κB signaling pathway in CC patients.
  • To determine the correlation between TAMs, signaling pathways, and Overall Survival (OS) in CC.
  • To analyze the impact of TAMs and related biomarkers on CC progression and patient outcomes.

Main Methods:

  • Retrospective analysis of 691 CC patients diagnosed via FIGO staging.
  • Tissue Microarray (TMA) and immunohistochemistry used to evaluate TAM infiltration and tumor progression biomarkers.
  • Kaplan-Meier and multivariable Cox regression analyses assessed the impact on recurrence-free (RF) and OS.

Main Results:

  • High CD163+204+ TAM density correlated with E-cadherin, Vimentin, MMP9, VEGFα, Bcl-2, Ki-67, CD25, MIF, FOXP3, and IL-17 expression via STAT3/NF-κB pathways (p < 0.0001).
  • Advanced TNM stage IV strongly associated with STAT3/NF-κB pathways, CD25, VEGFα, MIF, and Ki-67 (p < 0.001).
  • SNAIL (HR=1.52), E-cadherin (HR=1.78), and Ki-67 (HR=1.44) significantly influenced OS and recurrence survival.

Conclusions:

  • M2-TAMs and the STAT3/NF-κB pathway significantly drive CC tumor progression.
  • These factors correlate with severe clinicopathological findings in CC.
  • M2-TAMs and STAT3/NF-κB pathway activation represent critical indicators of poor prognosis in cervical carcinoma.