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Combining TIGIT Blockade with MDSC Inhibition Hinders Breast Cancer Bone Metastasis by Activating Antitumor Immunity
Lea Monteran1, Nour Ershaid1, Ye'ela Scharff1
1Department of Pathology, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Cancer Discovery
|March 1, 2024
Summary
Targeting granulocyte and T cell interactions, specifically TIGIT and IL1β, effectively reduced breast cancer bone metastasis in mice. This approach reactivated anti-tumor immunity and showed promise in human samples for treating bone metastasis.
Area of Science:
- Oncology
- Immunology
- Cancer Metastasis
Background:
- Bone metastasis is a frequent and incurable complication of breast cancer, leading to significant patient morbidity.
- The immune microenvironment in bone metastases plays a critical role in disease progression and therapeutic resistance.
Purpose of the Study:
- To investigate the dynamic immune changes during breast cancer bone metastasis using a mouse model.
- To identify key cellular and molecular players driving immunosuppression in the bone metastatic niche.
- To evaluate the therapeutic potential of targeting identified pathways in breast cancer bone metastasis.
Main Methods:
- Utilized an immunocompetent mouse model of spontaneous breast cancer bone metastasis.
- Performed immune transcriptome profiling of bone metastatic lesions and bone marrow at various stages.
- Analyzed immune cell interactions, focusing on granulocytes and T cells.
- Targeted specific signaling pathways (PD-1, TIGIT) and cytokines (IL1β) in vivo.
- Validated findings in human bone metastasis patient samples.
Main Results:
- Revealed dynamic immune transcriptome changes throughout the bone metastatic process.
- Identified significant cross-talk between granulocytes and T cells, creating an immunosuppressive microenvironment.
- Demonstrated that targeting TIGIT and IL1β pathways attenuated bone metastasis and improved survival by reactivating antitumor immunity.
- Confirmed the prominence of TIGIT and IL1β in human bone metastasis samples.
Conclusions:
- The interaction between granulocytes and T cells is crucial in shaping the immunosuppressive bone metastatic microenvironment.
- Cotargeting TIGIT and IL1β represents a promising therapeutic strategy to inhibit breast cancer bone metastasis.
- This approach holds potential for treating human bone metastasis by modulating the immune response.
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