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Immune Modulation with RANKL Blockade through Denosumab Treatment in Patients with Cancer
Hewitt Chang1, Jaqueline Marquez1, Brandon K Chen1
1Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, California.
Cancer Immunology Research
|January 26, 2024
Summary
Denosumab shows modest immune effects alone in cancer patients. However, combining denosumab with chemotherapy or steroids significantly alters immune cells and induces immune checkpoints.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Denosumab, a monoclonal antibody, targets receptor activator of NFκB ligand (RANKL).
- RANKL inhibition is used to prevent bone metastasis in cancer patients.
- RANK-RANKL interactions influence both bone turnover and immune cell regulation.
Purpose of the Study:
- To investigate the immunomodulatory effects of denosumab in cancer patients.
- To assess changes in circulating immune cells during denosumab treatment.
- To determine if concomitant therapies influence denosumab's immune effects.
Main Methods:
- Mass cytometry analysis of blood samples from cancer patients receiving denosumab.
- Comparison of immune cell profiles before and during denosumab treatment.
- Stratification of patients based on concurrent chemotherapy and/or steroid use.
Main Results:
- Denosumab monotherapy had minimal impact on circulating immune cell frequency and activation.
- Concomitant chemotherapy and/or steroids significantly enhanced immune modulation by denosumab.
- Increased natural killer cells, classical monocytes, and expression of immune checkpoints (CTLA-4, TIM3) were observed in combined treatment groups.
Conclusions:
- Denosumab exhibits modest immunomodulatory effects when used alone in cancer patients.
- Combination therapy with denosumab, chemotherapy, and/or steroids can induce significant immune modulation.
- Denosumab in combination with conventional treatments may enhance immune responses by inducing immune checkpoints.
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