Grace Hopper Distinguished Lecture: Melody Swartz, University of Chicago
March 6 at 3:30 PM - 4:30 PM
Abstract:
Immunoregulatory roles of lymphatic vessels in cancer and opportunities for immunoengineering
Tumor lymphangiogenesis, which involves both the activation and growth induction of surrounding lymphatic vessels, is well-known to correlate with tumor progression and metastasis in many solid tumors. While it is typically assumed that lymphangiogenesis supports an ‘escape route’ for cells to leave the primary tumor, the tumor-draining lymph node serves as the key site of immune surveillance. Our lab has been exploring how lymphatic involvement affects the tumor immune microenvironment and anti-tumor immunity while promoting metastasis at the same time. In doing so, we have discovered new fundamental roles for lymphatic endothelial cells (LECs) as direct modulators of immunity. This is important because LECs are constantly bathed with peripheral antigens, cytokines, danger signals and immune cells travelling from peripheral tissues to lymph nodes. In terms of promoting metastasis, we have learned that tumor-activated lymphatics alter the tumor microenvironment in multiple ways, including (i) increasing immune suppressive cell types and factors in the tumor microenvironment both directly and indirectly, (ii) inhibiting maturation of antigen-presenting cells and T cell activation, and (iii) driving changes in the stromal microenvironment that promote both cancer invasion and immune suppression. However, lymphatic activation also enhances communication with cells in the draining lymph node by antigen and cell transport, and leads to increased immune cell infiltration within the tumor. As a consequence, lymphangiogenic tumors can be exceptionally responsive to immunotherapy, paradoxically. This ‘lymphangiogenic potentiation’ of immunotherapy depends on tumor cell infiltration of both cross-presenting dendritic cells and naïve T cells, driving local T cell education post-immunotherapy and antigen spreading. On the translational side, we are engineering novel strategies to exploit lymphangiogenesis for cancer immunotherapy. Beyond cancer, our findings suggest that LECs may be potential targets for immunomodulation in vaccination, autoimmunity, and allergy.
Melody Swartz
William B. Ogden Professor of Molecular Engineering at the University of Chicago
Melody A. Swartz’s research is focused on the lymphatic system and aims to understand its role in immunity and pathophysiology, especially in cancer. Her lab draws on bioengineering approaches in cell biology and physiology, to investigate the role of lymphatic vessels in maintaining immunological tolerance and the role of lymphangiogenesis in controlling inflammation and immunity. Her lab applies this knowledge to develop novel immunotherapeutic approaches in cancer, including lymph node-targeting vaccine approaches, as well as in vitro model systems that recapitulate relevant features of the 3D, perfused tumor microenvironment.
Swartz obtained her BS from Johns Hopkins and PhD from MIT, both in Chemical Engineering, and carried out postdoctoral work at Harvard Medical School and the Brigham & Women’s Hospital. She started her independent career at Northwestern University in the Department of Biomedical Engineering and then spent 13 years at the Ecole Polytechnique Fédérale de Lausanne (EPFL) Institute of Bioengineering, where she eventually served as Institute Director. She then joined the newly formed University of Chicago’s Pritzker School of Molecular Engineering to help grow the field of immunoengineering there, and currently serves as co-director of the Chicago Immunoengineering Innovation Center. Among her honors and awards, she is a MacArthur Fellow and member of the National Academy of Engineering, National Academy of Medicine, and the American Academy of Arts and Sciences.