Clinical Report: Addressing Resistance to Immunotherapy in TNBC

Overview

This review evaluates mechanisms of resistance to immunotherapy in triple-negative breast cancer (TNBC), focusing on mast cell plasticity and metabolic reprogramming.

Background

Triple-negative breast cancer (TNBC) poses significant treatment challenges due to its aggressive nature and lack of targetable receptors. The introduction of immune checkpoint inhibitors (ICIs) has improved outcomes, yet resistance remains a major barrier to effective treatment.

Data Highlights

No numerical data or trial results were provided in the source material.

Key Findings

• Mast cells (MCs) exhibit high phenotypic diversity, with a unique subset known as antigen-presenting mast cells (apMCs) capable of priming anti-tumor T cell responses.
• Modulation of apMCs has been shown to enhance responses to anti-PD-1 therapy in patients with ICI-refractory TNBC.
• Metabolic dysregulation in TNBC skews MCs toward immunosuppressive phenotypes.
• A vicious cycle exists where metabolic reprogramming drives immunosuppressive phenotypes.
• Patient-derived organoid (PDO) models are emerging as a platform for studying metabolism-immune interactions in TNBC.
• Multidimensional therapeutic strategies are being explored to combat immunotherapy resistance.

Clinical Implications

Understanding these mechanisms may lead to more effective immunotherapy strategies for patients with TNBC.

Conclusion

This review provides insights into the interplay between mast cell plasticity and metabolic changes in TNBC.

Related Resources & Content

1. The ASCO Post, 2020 -- Immunotherapy for Triple-Negative Breast Cancer: An Evolving Story
2. The ASCO Post, 2024 -- New Computational Tool May Predict Immunotherapy Outcomes in Patients With Metastatic Breast Cancer
3. The ASCO Post, 2019 -- Resistance to Immune Checkpoint Blocker May Be Linked to Metabolic Imbalance
4. NCCN Guidelines® Insights: Breast Cancer, Version 5.2025 - PubMed
5. Mobilizing antigen-presenting mast cells in anti-PD-1-refractory triple-negative breast cancer: a phase 2 trial | Nature Medicine
6. The ASCO Post — Understanding the Role of Immune Function in the Treatment of HER2-Positive Breast Cancer
7. NCCN Guidelines® Insights: Breast Cancer, Version 5.2025 - PubMed
8. Mobilizing antigen-presenting mast cells in anti-PD-1-refractory triple-negative breast cancer: a phase 2 trial | Nature Medicine
9. Lactate metabolism and lactylation in breast cancer: mechanisms and implications | Cancer and Metastasis Reviews | Springer Nature Link