Abstract B72: CD8αα+ langerin+ dendritic cells maintain the effector CD8 T cell population after adoptive transfer.

Abstract

Abstract Adoptive cell transfer (ACT) is a promising new area of anti-cancer therapy. The process involves the isolation of T cells from a patient's blood, in vitro stimulation of the T cells against cancer antigens, then re-infusion of the activated cells back into the patient. This process provides a population of effector CD8 T cells capable of recognizing and killing cancer cells. ACT is currently limited by the ability of the transferred cells to survive in high numbers for an extended period of time and therefore overcoming this problem is a focus to improve the efficacy of the treatment. The activation of cancer-specific CD8 T cells is dependent on the ability of dendritic cells (DCs) to acquire and present exogenous antigens on major histocompatibility complex class I (a process known as cross-presentation) for the stimulation of CD8 T cells. We have previously found a subset of splenic DCs expressing the CD8αα homodimer and the c-type lectin receptor langerin (CD207), that have a strong ability to activate CD8 T cells by cross-presentation. This DC subset is found in the marginal zone of the spleen, is highly efficient at phagocytosing apoptotic cells from the blood, and is believed to play an important role in scanning the blood for antigens. We therefore hypothesized that CD8αα+ langerin+ DCs influence the survival and expansion of adoptively transferred effector CD8 T cells in the blood. Within this project we have used langerin-diphtheria toxin receptor mice, in which all langerin-expressing cells are ablated in vivo upon injection of diphtheria toxin, to address the role of the CD8αα+ langerin+ DC subset in maintaining the CD8 T cell population after ACT. For this purpose, we challenged mice intravenously with the T cell thymoma EG7.OVA and adoptively transferred in vitro activated OVA-specific CD8 T cells (OT-I T cells) 12 days later with or without prior langerin-DC depletion. We found a larger population of OT-I T cells when these were transferred into an EG7.OVA bearing host when compared to mice without tumors. Interestingly, mice that were depleted of their CD8αα+ langerin+ DCs did not develop this increase in OT-I T cell number and their absence resulted in reduced survival. Our data therefore suggest that antigen presentation by CD8αα+ langerin+ DCs play a role in sustaining high numbers of transferred CD8 T cells after ACT, resulting in increased protection against EG7.OVA. Manipulations that increase the stimulatory capacity of this DC subset could be a way to increase the efficacy of ACT therapy. Citation Format: John David Gibbins, Ian Hermans, Troels Petersen. CD8αα+ langerin+ dendritic cells maintain the effector CD8 T cell population after adoptive transfer. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B72.