Related Experiment Video
Updated: Jul 21, 2025
Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer
Published on: August 2, 2024
Matrix Metalloproteinase-9 Expression Is Associated with the Absence of Response to Neoadjuvant Chemotherapy in
Marylène Lejeune1, Laia Reverté1, Noèlia Gallardo1
1Oncological Pathology and Bioinformatics Research Group, Molecular Biology and Research Section, Pathology Department, Hospital de Tortosa Verge de la Cinta, Institut d'Investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili (URV), Esplanetes, 14, 43500 Tortosa, Spain.
Abstract:
Triple-negative breast cancer (TNBC) is particularly challenging due to the weak or absent response to therapeutics and its poor prognosis. The effectiveness of neoadjuvant chemotherapy (NAC) response is strongly influenced by changes in elements of the tumor microenvironment (TME). This work aimed to characterize the residual TME composition in 96 TNBC patients using immunohistochemistry and in situ hybridization techniques and evaluate its prognostic implications for partial responders vs. non-responders. Compared with non-responders, partial responders containing higher levels of CD83+ mature dendritic cells, FOXP3+ regulatory T cells, and IL-15 expression but lower CD138+ cell concentration exhibited better OS and RFS. However, along with tumor diameter and positive nodal status at diagnosis, matrix metalloproteinase-9 (MMP-9) expression in the residual TME was identified as an independent factor associated with the impaired response to NAC. This study yields new insights into the key components of the residual tumor bed, such as MMP-9, which is strictly associated with the lack of a pathological response to NAC. This knowledge might help early identification of TNBC patients less likely to respond to NAC and allow the establishment of new therapeutic targets.
Insights
Triple-negative breast cancer patients responding partially to neoadjuvant chemotherapy show better survival. Residual tumor microenvironment factors like MMP-9 indicate poor response, aiding early identification and new therapeutic targets.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- Triple-negative breast cancer (TNBC) presents a significant therapeutic challenge due to poor response rates and prognosis.
- The tumor microenvironment (TME) plays a critical role in modulating treatment effectiveness, particularly for neoadjuvant chemotherapy (NAC).
Purpose of the Study:
- To characterize the residual TME composition in TNBC patients post-NAC.
- To evaluate the prognostic implications of residual TME components in partial responders versus non-responders.
Main Methods:
- Immunohistochemistry and in situ hybridization were employed to analyze residual TME in 96 TNBC patients.
- Correlation analysis was performed to identify factors associated with NAC response and patient outcomes.
Main Results:
- Partial responders exhibited higher levels of CD83+ mature dendritic cells, FOXP3+ regulatory T cells, and IL-15, alongside lower CD138+ cell concentration, correlating with improved overall survival (OS) and relapse-free survival (RFS).
- Matrix metalloproteinase-9 (MMP-9) expression in the residual TME, along with tumor diameter and nodal status, independently predicted impaired NAC response.
Conclusions:
- Residual TME composition, particularly MMP-9 levels, provides critical insights into NAC response in TNBC.
- Identifying patients with poor pathological response to NAC early can guide treatment strategies and the development of novel therapeutic targets.
