Adoptive cellular therapy containing T cells and CD25+ NKT cells modulates myeloid cells and stimulates endogenous anti-tumor immune function (VAC7P.1038)

Abstract

Abstract Myeloid-derived suppressor cells (MDSCs) are a type of myeloid regulatory cell (Mreg) that suppresses the anti-tumor activity of immune effector cells. We have previously demonstrated that CD25+ NKT cells function as cellular adjuvants for converting MDSC into immune stimulatory myeloid cells, thereby rescuing anti-tumor T cell function from MDSCs in vitro. Here, we sought to characterize the in vivo efficacy of adoptive cellular therapy (ACT) utilizing reprogrammed T cells and CD25+ NKT cells in modulating MDSCs in FVBN202 mice. We demonstrate a significant 2-fold decrease in the frequency and absolute number of splenic MDSCs in recipients of ACT compared with control mice bearing comparable lung metastases. We also observed a significant 2-fold increase in the frequency and absolute number of mature myeloid cells (CD11b-MHC-II+CD40+CD86+). Functional analysis was performed in which CD11b- myeloid cells from ACT-recipient animals bearing lung metastases were cultured with autologous splenocytes. CD11b- MHC II+ cells induced a significant release of splenocyte-derived IFN-γ; this response was enhanced greater than 20-fold upon the addition of tumor cells. Importantly, ACT recipients of mice bearing Ki-67hi circulating tumor cells experienced extended time to progression compared to control animals. These data suggest CD25+ NKT cells may act to promote ‘vaccination in situ’ of endogenous T cells, in addition to boosting anti-tumor efficacy of ACT.