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A Predictive Immunological Signature Associated with Pathological Response in Breast Cancer Treated with Neoadjuvant
Luis Arturo Palafox-Mariscal1, Mariel García-Chagollán2, Jesús García-Gómez3
1División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44340, Jalisco, Mexico.
Biomedicines
|March 28, 2026
Summary
Tumor immune balance, like the CD8/CD4 T cell ratio, predicts response to neoadjuvant chemotherapy (NACT) in breast cancer. These immune features are more effective than molecular profiles alone for predicting pathological response.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Breast cancer heterogeneity impacts treatment response.
- Tumor-infiltrating lymphocytes (TILs) are crucial for therapeutic efficacy, especially with neoadjuvant chemotherapy (NACT).
- Tumor microenvironment composition varies significantly, necessitating advanced analytical methods.
Purpose of the Study:
- To explore immune cell infiltration in locally advanced breast cancer.
- To investigate the relationship between the tumor microenvironment and NACT response.
- To identify predictive biomarkers for pathological response to NACT.
Main Methods:
- Utilized next-generation sequencing (NGS) for immune cell deconvolution.
- Employed automated immunohistochemistry (IHC) on biopsies.
- Quantified CD4+, CD8+ T cells, and immune checkpoint markers (FoxP3, LAG3, CTLA4, PD1, TIM-3).
Main Results:
- Transcriptomic analysis indicated a cytotoxic tumor environment correlates with chemosensitivity.
- Individual immune cell markers and checkpoint expression did not significantly differ between response groups.
- Tumor immune microenvironment organization and coordination showed distinct associations with chemosensitivity.
Conclusions:
- Immune balance metrics, such as the CD8/CD4 ratio, are potential predictors of pathological response to NACT.
- T cell-contextualized immune features outperformed molecular phenotype in predicting response in this cohort.
- Understanding immune microenvironment dynamics is key for optimizing breast cancer therapy.
