GSE248774 Immune modulation with RANKL-blockade through denosumab treatment in cancer patients

We examined whether administering denosumab could modify modulate circulating immune cells in c ancer patients. Blood was collected from 23 prostate cancer patients and 3 renal cell carcinoma patients, who provided written informed consent, with advanced disease who were receiving denosumab, prior to and during denosumab treatment. Using high-dimensional mass cytometry, we found that denosumab treatment by itself induced modest effects on circulating immune cell frequency and activation. We also found minimal changes in the circulating T cell repertoire and the frequency of new thymic emigrants with denosumab treatment. However, when we stratified patients by whether they were receiving chemotherapy and/or steroids, patients receiving these concomitant treatments showed significantly greater immune modulation, including an increase in the frequency of NK cells early and classical monocytes later. We also saw broad induction of CTLA-4 and TIM3 expression in circulating lymphocytes a nd some monocyte populations. These findings suggest that denosumab treatment by itself has modest immunomodulatory effects, but when combined with conventional cancer treatment, can lead to the induction of immunologic checkpoints.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Other Homo sapiens Source Type: research