BME Seminar: Dr. Melody A. Swartz - Lymphatic Vessels in Inflammation and Cancer: Linking Mechanobiology with Immune Regulation

Armour Colege of Engineering's Biomedical Engineering Department will host a seminar featuring Melody Swartz, Ph.D., Professor at The Institute of Molecular Engineering at University of Chicago on March 6, 2015. Lecture topic will be Lymphatic Vessels in Inflammation and Cancer: Linking Mechanobiology with Immune Regulation.

Abstract

In tissues, interstitial fluid flow is mechanically coupled to lymphatic drainage, and both are often increased in acute inflammation and 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 downstream lymphatic pump function. Still, 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-tuning of the transport of antigens, cells, and chemokines to the local lymph node. But why does lymphatic transport need to be actively regulated if its primary function is to drain excess fluid from the interstitium to prevent swelling? In exploring this question, we are finding lymphatic transport to play fundamental roles in fine-tuning immune responses and regulating the presentation of abundant self-antigens for deleting autoreactive T cells. At the same time, inflammatory lymphangiogenesis coupled with increased interstitial flow drives fibroblast activation and stromal changes that promote matrix alignment and stiffening as well as, simultaneously, immune suppression. In the tumor microenvironment, these factors synergize to promote escape from host immunity, presumably necessary for metastasis. Together, these findings help to define new immunomodulatory roles for lymphatic vessels in inflammation and cancer.