The Capacity Of Cd4(+) V Gamma 9v Delta 2 T Cells To Kill Cancer Cells Correlates With Co-Expression Of Cd56

Human V gamma 9V delta 2 T cells are a unique T-cell type, and data from recent studies of V gamma 9V delta 2 T cells emphasize their potential relevance to cancer immunotherapy V gamma 9V delta 2 T cells exhibit dual properties since they are both antigenpresenting cells and cytotoxic toward cancer cells. The majority of V gamma 9V delta 2 T cells are double-negative for the coreceptors CD4 and CD8, and only 20-30% express CD8. Even though they are mostly neglected, a small fraction of V gamma 9V delta 2 T cells also express the co-receptor CD4. Here the authors show that CD4(+) V gamma 9V delta 2 T cells comprise 0.1-7% of peripheral blood V gamma 9V delta 2 T cells. These cells can be expanded in vitro using zoledronic acid, pamidronic acid or CD3 antibodies combined with IL-2 and feeder cells. Unlike most conventional CD4(+) ab T cells, CD4(+) V gamma 9V delta 2 T cells are potently cytotoxic and can kill cancer cells, which is here shown by the killing of cancer cell lines of different histological origins, including breast cancer, prostate cancer and melanoma cell lines, upon treatment with zoledronic acid. Notably, the killing capacity of CD4(+) V gamma 9V delta 2 T cells correlates with co-expression of CD56. (C) 2021 International Society for Cell & Gene Therapy. Published by Elsevier Inc.