Role of IL-18 on the activation of Vδ₂⁺ T cells – For the development of novel cancer immunotherapy –

Abstract

IL(interleukin)-18 is known to induce proliferation of Vδ₂⁺ T cells and expression of CD56, resulting in enhancement of cytotoxic activity. We focused on the expression of CD56 and the direct action of IL-18 on Vδ₂⁺ T cells to evaluate the importance of IL-18 for developing Vδ₂⁺ T cells-based adoptive immunotherapy. Peripheral blood mononuclear cells (PBMCs) were purified from heparinized blood of healthy donors and cancer patients. CD56⁻ Vδ₂⁺ T cells isolated from healthy subjects were cultured with IL-2 and IL-18 or with IL-2 alone. The number of CD56⁻ Vδ₂⁺ cells increased compared with those with IL-2 alone. However, this increase was not statistically significant. CD56⁻ Vδ₂⁺ T cells derived from CD56⁺-depleted PBMCs were stimulated by phosphoantigens and cultured with IL-2 and IL-18, and showed significantly stronger cytotoxic activity than resultant CD56⁺ Vδ₂⁺ T cells. IL-18 promotes the proliferation of Vδ₂⁺ T cells from PBMCs of ovarian cancer patients. Thus, IL-18 is worth to be considered as a strong candidate in the development of effective cancer immunotherapy.