Immune monitoring of neoadjuvant chemo-immunotherapy for triple-negative breast cancer

Fatima Munnawara Syeda¹Rita Antunes Santos²Luana Madalena Sousa³Ana Raquel Paiva²Noémia Castelo Branco²Tatiana Cunha Pereira²Gabriela Sousa²Paulo Rodrigues-Santos^4*

• ¹University of Coimbra, Faculty of Medicine, Coimbra, Portugal
• ²Instituto Portugues de Oncologia de Coimbra Francisco Gentil EPE, Coimbra, Portugal
• ³Universidade de Coimbra Centro de Neurociencias e Biologia Celular, Coimbra, Portugal
• ⁴Instituto de Imunologia, Institute of Immunology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal

Abstract Triple-negative breast cancer (TNBC) is an aggressive subtype defined by the absence of estrogen receptor, progesterone receptor, and HER2 expression. It accounts for 10–20% of breast cancer cases, predominantly affecting younger women, and is associated with poor prognosis due to high recurrence rates and limited therapeutic options. Past treatment strategies relied solely on chemotherapy, but challenges such as metastatic potential and chemoresistance persisted. Recent advancements in neoadjuvant chemo-immunotherapy aim to address these limitations by combining chemotherapy with immune checkpoint inhibitors, with promising clinical trial results demonstrating improved response rates and survival outcomes. A central focus is placed on biomarker-based immune monitoring strategies, encompassing both tissue-based biomarkers—such as programmed cell death ligand 1 (PD-L1) expression, microsatellite instability, tumor mutational burden, tumor-infiltrating lymphocytes (TILs), and gene expression signatures—and blood-based biomarkers, including gene expression profiling, comprehensive immunophenotyping, and cytokine profiling. In addition, an emerging role of advanced imaging technologies, such as immuno-positron emission tomography (immuno-PET) and radiomics, could permit real-time immune monitoring. This review aims to provide a comprehensive overview of the current landscape of immune monitoring in TNBC, highlighting its challenges, predictive and prognostic value, and potential to guide clinical decision-making. By addressing key immune response biomarkers, technical limitations, and emerging technologies, we seek to outline strategies for optimizing treatment and enhancing personalized medicine approaches for TNBC patients. Future integration of innovative monitoring techniques holds promise for improving patient outcomes.