The Ruhland lab is broadly interested in understanding the who, what, when and where of antigen presentation in the lymph node. In particular we focus on the pathways used by myeloid cell populations to bring tumor-derived antigen into the lymph node and subsequently seed antigen into lymph node resident cell populations. Our studies have found that who receives the antigen in the lymph node has important downstream impacts on the effectiveness of anti-tumor T cell priming. In complementary studies, we find that the source (i.e. what) of the antigen (bacterial, self-derived, tumor-derived) influences the ability of the antigen to propagate widely and thus restricts where the different types of myeloid cells can present antigen to T cells. Importantly, we find that these patterns of antigen dissemination change when inflammation is present in the peripheral tissue which suggests this is a programmable process vulnerable to therapeutic intervention. Our work has important implications for both cancer immunotherapy as well as the treatment of autoimmune disease; in each case the ability to fine-tune the characteristics of antigen presentation would mark a novel intervention point for therapy.
Our approaches involve the use of transgenic mouse models, advanced high-resolution imaging, including multiphoton live imaging, and flow cytometry. We use fluorescent reporter mice and tumor cell lines to track antigen in vivo and in vitro and use a combination of immune cell-based assays to interrogate function. Together we design systems to address complex lymph node biology with the goal of optimizing the immune response.