Enhanced levels of endogenous common γ chain receptor cytokines influence CD8 T cell subpopulation numbers and phenotype in cancer patients receiving CD4 T cell immunotherapy: Observations In Four Cases Of Patients With Ovarian Cancer (46.31)

Abstract

Abstract The common γ chain receptor family of cytokines have been associated with T cell homeostasis, development and survival. In this study, we assessed the therapeutic effects of adoptively transferred CD4 T cells and their affects on endogenous expression of such cytokines in patients with ovarian cancer. Using MUC1 peptide and IL-2 for ex vivo CD4 effector cell generation, we show that 3 monthly treatment cycles of autologous T cell restimulation and local intraperitoneal reinfusion resulted in diminished serum CA125 tumor marker levels and enhanced patient survival. One patient remains disease free, another patient experienced prolonged survival for nearly 16 months with recurrent disease and two patients expired within 3-5 months following treatment. Prolonged survivors showed lower levels of systemic memory (CD8+CD45RO+)/naïve (CD8+CD45RA+) CD8 T cell ratios when compared to that of short-term survivors. Such subpopulations among prolonged survivors were predominantly FoxP3-NEG and at relatively greater levels when compared to that of corresponding pre-treatment conditions. Lastly, peptide-restimulated PBMCs from these patients showed variable gene expression levels of pre- and post-treatment IL-15, IL-21 and IL-9 that were further associated with prolonged and/or disease-free survival. This suggests that CD4 cell transfer may induce levels of endogenous cytokines associated with CD8 survival and/or homeostasis that may contribute to enhanced CD4 therapeutic potentials