Tumor-Associated Neutrophils and Desmoplastic Reaction in the Breast Cancer Tumor Microenvironment: A Comprehensive Review
by
, and
Stavroula Papadopoulou
, 
Vasiliki Michou
*
,
Arsenios Tsiotsias
,
Maria Tzitiridou-Chatzopoulou
and
Panagiotis Eskitzis
Department of Midwifery, School of Healthcare Sciences, University of Western Macedonia, Keptse, 50200 Ptolemaida, Greece
*
Author to whom correspondence should be addressed.
Cancers 2026, 18(3), 404; https://doi.org/10.3390/cancers18030404
Submission received: 20 December 2025
/
Revised: 17 January 2026
/
Accepted: 22 January 2026
/
Published: 27 January 2026
(This article belongs to the Section Tumor Microenvironment)
Simple Summary
Breast cancer progression is strongly influenced by the tumor microenvironment, particularly by tumor-associated neutrophils (TANs) and the desmoplastic reaction (DR), a fibrotic stromal response. Increasing evidence shows that TANs and DR engage in a bidirectional, self-reinforcing interaction that promotes tumor growth, immune evasion, metastasis, and resistance to therapy. Pro-tumorigenic TANs enhance angiogenesis, extracellular matrix remodeling, and immunosuppression, while desmoplastic stroma increases tissue stiffness and limits immune cell infiltration and drug delivery. Significantly, immature desmoplastic patterns are associated with clinically aggressive breast cancer subtypes with poor prognosis and high TAN infiltration. This review highlights how TAN plasticity and stromal remodeling jointly shape disease progression and discusses emerging therapeutic strategies that target both immune and stromal components of the tumor microenvironment to improve outcomes in breast cancer.
Abstract
The evolving tumor microenvironment (TME) plays a critical role in breast cancer tumorigenesis, growth, and metastatic potential. This study focuses on two key components of the TME: tumor-associated neutrophils (TANs) and the desmoplastic reaction (DR). We will analyze their multifaceted functions, emphasizing the significant mutual relationships among them, which dramatically affect disease outcomes and the effectiveness of treatments. TANs can either suppress or promote tumors, demonstrating notable functional flexibility in response to signals from their immediate environment. Concurrently, the proliferation of myofibroblasts and the extensive deposition of extracellular matrix (ECM), which characterize the DR, substantially alter the tumor’s physical properties, increasing its stiffness. This increased stiffness significantly obstructs immune system cells from accessing the tumor, ultimately limiting the effectiveness of therapies and contributing to a more clinically aggressive tumor behavior. A comprehensive understanding of the interactions among TANs, the desmoplastic stroma, and other elements of the TME is critical for developing new predictive biomarkers and establishing more effective targeted therapies.
