Host type I IFN signals mediate awareness of tumor and promote adaptive immune responses against tumor antigens

MERCEDES BEATRIZ FUERTES; JUSTIN KLINE; THOMAS GAJEWSKI; AALOK KACHA

Chicago, IL, Estados Unidos

Conferencia; 37º Autumn Immunology Conference; 2008

Emerging data suggests that the innate immune system plays an important role in the priming of anti-tumor T cells. Gene expression profiling of human melanoma metastases revealed the presence of an IFN signature in T cell-containing tumors. Mechanistic experiments were performed in murine models studying the role of host type I IFNs in bridging to T cell priming. Following subcutaneous implantation of B16 melanoma cells in B6 mice, IFN-b was induced in the tumor draining lymph nodes within 3-5 days. This preceded detection of a tumor antigen-specific CD8+ T cell response. In Stat1 ko mice defective in IFN-based signaling or in type I IFNR ko mice, T cell priming and tumor rejection were blunted.  Bone marrow chimera experiments revealed a requirement for IFN signaling in the hematopoietic compartment.  Adoptive transfer experiments with WT TCR Tg T cells or immunization with WT antigen-pulsed DCs pointed to a type I IFN-dependent effect at the levels of APCs. Our results indicate that IFN-b induction is part of the innate immune recognition of a growing tumor, which is necessary for priming of anti-tumor T cells.  Exploitation of the IFN-b system could lead to improved anti-tumor immunity in vivo by augmenting spontaneous adaptive immune responses.