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Identification of Functional Immune Biomarkers in Breast Cancer Patients
Roshanak Derakhshandeh1, Yuyi Zhu1, Junxin Li1
1Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
International Journal of Molecular Sciences
|November 27, 2024
Summary
Natural killer T (NKT) cells are reduced in breast cancer patients but often remain functional. Loss of NKT cell function, not just number, impacts anti-tumor immunity, suggesting potential therapeutic targets.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- Cancer immunotherapy shows promise, especially in hematological cancers, but has limited efficacy in breast cancer, potentially due to immune-suppressive tumor microenvironments.
- Natural killer T (NKT) cells are crucial for immune surveillance and are often depleted in cancer patients.
- NKT cell function may serve as a biomarker to predict response to immune cell-based therapies in breast cancer.
Purpose of the Study:
- To develop a quantitative method for assessing NKT cell function in breast cancer patients.
- To evaluate the relationship between NKT cell number, function, and response to immunotherapy.
- To investigate mechanisms of NKT cell suppression by breast tumors and identify potential therapeutic interventions.
Main Methods:
- Developed a quantitative assay using artificial antigen-presenting cells and real-time PCR for IFN-γ to measure NKT cell function.
- Compared NKT cell numbers and function in breast cancer patients versus healthy donors.
- Analyzed tumor-infiltrating lymphocytes, PD-L1 expression, and immune gene signatures (TNFα, LAG3, LIGHT) in low and high NKT responders.
- Investigated the role of immunosuppressive lipids secreted by breast tumors.
Main Results:
- Breast cancer patients showed reduced circulating NKT cell numbers, but most retained functional NKT cells.
- Functional loss of NKT cells, rather than reduced numbers, was more significantly associated with poor immune response.
- Low NKT responders exhibited decreased induction of IFN-γ, TNFα, LAG3, and LIGHT.
- Breast tumors secrete immunosuppressive lipids that inhibit NKT cell responses.
Conclusions:
- NKT cell function is a critical indicator for predicting response to immune-based therapies in breast cancer.
- Targeting lipid metabolism pathways may restore NKT cell function and enhance anti-tumor immunity in breast cancer.
- NKT cell functional assays can guide patient selection for immunotherapies.
