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Updated: Jan 23, 2026
09:29
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
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Interferon Signaling Is Diminished with Age and Is Associated with Immune Checkpoint Blockade Efficacy in
Jaclyn Sceneay1,2, Gregory J Goreczny1,2, Kristin Wilson1
1Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Cancer Discovery
|June 21, 2019
Summary
Aging impairs immune checkpoint blockade (ICB) therapy effectiveness in triple-negative breast cancer (TNBC). Restoring innate immune function with a STING agonist improved ICB response in aged mice, suggesting new therapeutic strategies.
Area of Science:
- Immunology
- Oncology
- Aging Research
Background:
- Immune checkpoint blockade (ICB) therapy has transformed cancer treatment, particularly for triple-negative breast cancer (TNBC) due to its immunogenicity.
- TNBC affects women across all age groups, but the impact of aging on ICB efficacy remains unclear.
Purpose of the Study:
- To investigate how age-related immune dysfunction affects ICB efficacy in TNBC.
- To explore potential strategies to overcome age-associated resistance to ICB therapy.
Main Methods:
- Utilized aged TNBC-bearing mouse models to assess ICB response.
- Analyzed the tumor microenvironment for immune signaling pathways, including IFN signaling and antigen presentation.
- Administered a STING agonist to prime innate immunity in aged mice.
Main Results:
- Increased immune dysfunction with age was found to limit ICB efficacy in aged TNBC mice.
- The tumor microenvironment in aged mice and human TNBC patients showed reduced IFN signaling and antigen presentation.
- STING agonist treatment restored ICB response in aged mice by enhancing innate immune activation.
Conclusions:
- Age-related immune dysfunction is a significant mechanism of ICB resistance in TNBC.
- Assessing IFN-related genes may help identify TNBC patients who could benefit from combination therapy with ICB and an IFN pathway activator.
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