Abstract 2541: Differential trafficking of dendritic cells after immunization determines establishment of systemic anti-tumor responses

Abstract

Abstract Systemic immune activation and memory cell generation is desired in dendritic cell (DC)-based therapies against cancers, especially with metastasis. Migration properties of DCs, however, could limit the responses regionally constrained. Clinically, DC-vaccines are often given subcutaneously (s.c.), intravenously (i.v.) or intradermally (i.d.), without monitoring the migration of DCs. In this study, we visualized trafficking of DCs labeled with In-111 oxine using a whole-body micro-SPECT imager after immunization via different routes and examined induction of immune activation and memory cell generation in mice. Bone marrow-derived DCs were used. Surprisingly, most of s.c. transferred DCs failed to migrate to the adjacent lymph nodes (LNs) and died at the injection site, irrespective of their maturation status. DCs injected i.v. were initially trapped in the lungs, but gradually migrated to the spleen, liver and, to a lesser extent, LNs. In contrast, DCs administered i.d. and intraperitoneally (i.p.) quickly entered lymphatic system and distributed to LNs. Proliferation of CMFDA labeled OT-1 CD8 T cells pre-transferred to mice receiving ovalbumin loaded DCs (OVA-DCs) indicated that i.v. and i.p. immunizations triggered stronger and more systemic expansion of effector T cells than s.c. and i.d. immunizations. To examine the establishment of long-term defense, we next immunized mice with OVA-DCs and challenged them with OVA-expressing tumors intramuscularly, contra-lateral to the s.c. and i.d. injection site. Intriguingly, i.v. immunization seemed less effective than the others in developing long-term antigen-specific immunity, despite its capability to induce an extensive acute responses. These results might suggest that difference in the microenvironment of organs where CD8 T cells encounter the antigen (i.e., spleen or LNs) controls the generation of long-lived memory cells. Collectively, immunization route would be a critical factor that determines the spatial distribution of immune activation and generation of functional memory cells in DC-based therapies. Citation Format: Noriko Sato, Kingsley Asiedu, Peter L. Choyke. Differential trafficking of dendritic cells after immunization determines establishment of systemic anti-tumor responses. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2541. doi:10.1158/1538-7445.AM2014-2541