NK cells in breast cancer
Andréa Massidda1, Santiago Moragon-Terencio2, Camille Baudesson de Chanville1
1Aix Marseille Université, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie de Marseille-Luminy, Marseille, France.
Trends in Immunology
|August 13, 2026
Summary
Natural killer (NK) cells show limited effectiveness in breast cancer due to tumor microenvironment constraints. New immunotherapies can potentially overcome these barriers to restore anti-tumor immunity.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Natural killer (NK) cells are crucial for innate antitumor immunity.
- Their therapeutic application in solid tumors, particularly breast cancer, is limited.
- NK cells are present in breast tumors but exhibit reduced cytotoxic activity.
Purpose of the Study:
- To investigate the reasons behind NK cell dysfunction in breast cancer.
- To identify the multilayered constraints imposed by the tumor ecosystem on NK cells.
- To explore novel immunotherapy strategies for enhancing NK cell function.
Main Methods:
- Utilized single-cell and spatial profiling techniques.
- Analyzed the impact of soluble mediators, metabolic pressures, and stromal architecture.
- Investigated the role of suppressive immune networks in reprogramming NK cells.
Main Results:
- NK cell failure in breast cancer is due to complex tumor ecosystem constraints, not immune absence.
- Soluble factors, metabolic challenges, stromal components, and immune networks reprogram NK cells.
- These factors uncouple NK cell activation from their cytotoxic function.
Conclusions:
- Breast cancer serves as a model for understanding innate immune dysfunction.
- Targeting tumor microenvironment constraints offers new avenues for immunotherapy.
- Reestablishing NK cell function is a promising strategy for improving breast cancer treatment.
