Lymphatic vessels in inflammation and cancer: Linking mechanobiology with immune regulation

MELODY SWARTZ, UNIVERSITY OF CHICAGO

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 also discovered some fundamental 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.

February 16th, 2017 at 12:15 PM in Clark Center Seminar Room S360

Hosted by:

Annelise Barron, Associate Professor of Bioengineering, Stanford University

Pre-Seminar February 14th, 2017 at 12:15 PM in Clark S361