Lymphatic Vessels in Inflammation and Cancer: New Roles in Immune Regulation and Implications for Immunotherapy
William B. Ogden Professor, Institute for Molecular Engineering
The University of Chicago
March 9, 2017
12:30 p.m. - 1:20 p.m.
Foege N130A, Wallace H. Coulter Seminar Room
In tissues, interstitial fluid flow is mechanically coupled to lymphatic drainage, and both are often increased in acute inflammation as well as in the tumor microenvironment where steeper-than-normal pressure gradients exist at the tumor margin due to higher fluid pressure in tumors. It has long been assumed that local lymph formation is driven primarily by pressure gradients generated by interstitial fluid stress and downstream lymphatic pump function, but we have found that vesicular transendothelial transport also contributes significantly to lymph formation and is actively regulated by the lymphatic endothelium according to inflammatory stimuli, allowing fine control of the delivery of antigens, cells, and chemokines to the local lymph node. While exploring why such delivery would need active control by lymphatic endothelial cells, we found new roles that the lymphatic endothelium plays in the regulating immunity, including direct antigen presentation to T cells. In some types of inflammation, local lymphatic expansion and activation occurs, in turn changing the biomechanical and cytokine environments that alter the immune microenvironment. For example, in some cancers, we found that tumor-associated lymphangiogenesis leads to the activation of TGF-and increased interstitial flow, both of which promote fibroblast differentiation and matrix remodeling. Lymphatic activation also triggers the release of cytokines that attract immune cells that, together with TGF-can promote an immune suppressive microenvironment and help the tumor escape from host immunity. Finally, our lab is exploring ways to translate this new knowledge towards strategies for immunotherapy.
Melody A. Swartz is the William B. Ogden Professor in the Institute of Molecular Engineering at the University of Chicago, where she holds a joint appointment in the Ben May Department for Cancer Research. She holds a BS from the Johns Hopkins University, and a PhD from Massachusetts Institute of Technology. She undertook postdoctoral studies at Brigham & Women’s Hospital in Boston before starting in 1999 as an Assistant Professor at Northwestern University, jointly in the Departments of Biomedical Engineering and Chemical Engineering. In 2003, she was recruited to the Ecole Polytechnique Fédérale de Lausanne (EPFL), where she was promoted to Full Professor in the Institute of Bioengineering and the Swiss Institute for Experimental Cancer Research. Her lab applies this knowledge to develop novel immunotherapeutic approaches in cancer, including lymph node-targeting vaccine approaches.