Cancer-associated fibroblasts from cervical cancer modulate protumoral neutrophil functions: evidence from a pilot exploratory study
- 1Universidad de Guadalajara, Centro Universitario de Ciencias de la Salud, Departamento de Microbiología y Patología, Instituto de Investigación en Cáncer e Infecciones
- 2Universidad de Guadalajara, Centro Universitario de Ciencias de la Salud, Departamento de Disciplinas Filosóficas, Metodológicas e Instrumentales
- 3Universidad de Guadalajara, Centro Universitario de Ciencias de la Salud, Departamento de Biología Molecular
Abstract
Cancer-associated fibroblasts (CAFs) are key regulators of the tumor microenvironment; however, their role in modulating neutrophil function during cervical cancer (CC) progression remains poorly understood. In this study, we evaluated whether CAF supernatants (CSN) derived from early (FIGO I–II) and late stages (FIGO III–IV) of CC differentially regulate neutrophil activity. Peripheral blood neutrophils from healthy donors were stimulated with CSN, and their functional responses were assessed, including cytokine production, metabolic activity (MTT), reactive oxygen species (ROS) generation, apoptosis and survival analyses, expression of activation (CD66b) and protease degranulation markers (MMP9 and NE), and neutrophil extracellular trap (NET) release. CSN factors promoted a predominantly proinflammatory cytokine profile in neutrophils, characterized by increased production of IL-6, IL-8, TNF-α, and IFN-γ. Additionally, stimulation with CAF enhanced neutrophil metabolic activity, ROS production, survival, and expression of CD66b, MMP9, and neutrophil elastase, suggesting preliminary stage-associated differences in neutrophils responses between CAFs derived from early- and late-stage tumors. Notably, NET formation was significantly higher in neutrophils stimulated with early-stage CAFs, whereas late-stage CAFs induced a metabolically active but lower NETosis release. These exploratory findings suggest that cervical cancer-derived CAFs may differentially modulate neutrophil functional responses according to tumor stage, highlighting the CAF-neutrophil axis as a potentially relevant component of the cervical cancer microenvironment.
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BibTeX
@article{resendizcastillo2026cancerassociated,
title = {{Cancer-associated fibroblasts from cervical cancer modulate protumoral neutrophil functions: evidence from a pilot exploratory study}},
author = {Luis Javier Reséndiz-Castillo and Marcela Guadalupe Martínez-Barajas and Ahtziri Socorro Carranza-Aranda and Jonathan René García-Bernal and Carlos Daniel Díaz-Palomera and Adrián Ramírez-de-Arellano and Moisés Ramos-Solano and Natali Vega-Magaña and Julio César Villegas-Pineda and Ana Laura Pereira-Suárez},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1900567},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1900567/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Cancer-associated fibroblasts from cervical cancer modulate protumoral neutrophil functions: evidence from a pilot exploratory study
AU - Luis Javier Reséndiz-Castillo
AU - Marcela Guadalupe Martínez-Barajas
AU - Ahtziri Socorro Carranza-Aranda
AU - Jonathan René García-Bernal
AU - Carlos Daniel Díaz-Palomera
AU - Adrián Ramírez-de-Arellano
AU - Moisés Ramos-Solano
AU - Natali Vega-Magaña
AU - Julio César Villegas-Pineda
AU - Ana Laura Pereira-Suárez
PY - 2026
DA - 2026/10/09
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1900567
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1900567/full
AB - Cancer-associated fibroblasts (CAFs) are key regulators of the tumor microenvironment; however, their role in modulating neutrophil function during cervical cancer (CC) progression remains poorly understood. In this study, we evaluated whether CAF supernatants (CSN) derived from early (FIGO I–II) and late stages (FIGO III–IV) of CC differentially regulate neutrophil activity. Peripheral blood neutrophils from healthy donors were stimulated with CSN, and their functional responses were assessed, including cytokine production, metabolic activity (MTT), reactive oxygen species (ROS) generation, apoptosis and survival analyses, expression of activation (CD66b) and protease degranulation markers (MMP9 and NE), and neutrophil extracellular trap (NET) release. CSN factors promoted a predominantly proinflammatory cytokine profile in neutrophils, characterized by increased production of IL-6, IL-8, TNF-α, and IFN-γ. Additionally, stimulation with CAF enhanced neutrophil metabolic activity, ROS production, survival, and expression of CD66b, MMP9, and neutrophil elastase, suggesting preliminary stage-associated differences in neutrophils responses between CAFs derived from early- and late-stage tumors. Notably, NET formation was significantly higher in neutrophils stimulated with early-stage CAFs, whereas late-stage CAFs induced a metabolically active but lower NETosis release. These exploratory findings suggest that cervical cancer-derived CAFs may differentially modulate neutrophil functional responses according to tumor stage, highlighting the CAF-neutrophil axis as a potentially relevant component of the cervical cancer microenvironment.
SN - 1664-3224
ER -