Monitoring circulating γδ T cells in cancer patients to optimize γδ T cell-based immunotherapy

The success of gamma delta T cell-based immunotherapy, where the cytotoxic activity of circulating gamma delta T lymphocytes is activated by nitrogen-containing bisphosphonates (n-BP), or possibly by bispecific antibodies or the combination of both, requires a profound knowledge of patients' gamma delta T cells. A possible influence of radio- or chemotherapy on gamma delta T cells as well as their reported exhaustion after repetitive treatment with n-BP or their lack of response to various cancers can be easily determined by the monitoring assays described in this perspective article. Monitoring the absolute cell numbers of circulating gamma delta T cell subpopulations in small volumes of whole blood from cancer patients and determining gamma delta T cell cytotoxicity using the Real-Time Cell Analyzer can give a more comprehensive assessment of a personalized tumor treatment. Possible future directions such as the combined usage of n-BP or phosphorylated antigens together with bispecific antibodies that selectively target gamma delta T cells to tumor-associated antigens, will be discussed. Such strategies induce expansion and enhance gamma delta T cell cytotoxicity and might possibly avoid their exhaustion and overcome the immunosuppressive tumor microenvironment.