2021 Otto Schmitt Lecture (Swartz) | Institute for Engineering in Medicine Archives

“Immunoregulatory Roles of Lymphatic Vessels in Cancer and Opportunities for Immunoengineering”

12:00 - 1:00 PM
Tuesday, October 26, 2021
Coffman Memorial Union

Abstract

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.

BIO

Melody A. Swartz is the William B. Ogden Professor in the Pritzker School of Molecular Engineering at the University of Chicago, where she holds a joint appointment in the Ben May Department for Cancer Research and is a member of the Committee on Immunology. She obtained her BS from Johns Hopkins and her PhD from MIT, both in chemical engineering, and carried out postdoctoral work at the Brigham & Women’s Hospital. She was an Assistant Professor of Biomedical Engineering at Northwestern University before moving to the EPFL in Lausanne, Switzerland, where she eventually served as the Director of the Institute for Bioengineering.

Dr. Swartz’s research focuses on elucidating and exploiting the roles of lymphatic function as it relates to cancer and chronic inflammatory diseases, using a variety of interdisciplinary approaches from bioengineering, immunobiology, physiology, cell biology and biomechanics. Her lab works in both basic hypothesis-driven research as well as in translational applications. A major interest has been to understand the immunological implications of lymphangiogenesis in tumors and other chronic inflammatory conditions, including allergic airway disease, and translating this basic research towards developing novel strategies for targeting the lymphatics and sentinel lymph nodes for immunotherapy. Building novel, physiologically relevant, 3D model systems for recapitulating key features of interest in lymph node and/or tumor microenvironments is an important part of this research program. Swartz is a MacArthur Fellow and a member of the National Academy of Medicine and the American Academy of Arts & Sciences.