As an inaugural CRI Lloyd J. Old STAR, Dr. Amanda Lund aims to develop a better understanding of how the lymphatic vessels influence immune responses against tumors as well as strategies that can exploit those insights to improve immunotherapy’s effectiveness.
Modern immunotherapy strategies have drastically improved survival for patients with metastatic melanoma, in addition to several other types of advanced cancers. However, not all patients respond to immunotherapy, and therefore we need to further understand how the immune system is activated in the context of cancer, especially melanoma. Lymphatic vessels are required to activate T cells and yet we know very little about how tumor-induced changes in lymphatic vessels alter T cell responses. Dr. Lund has already found that the growth of lymphatic vessels in and around tumors directly influences inflammation, immune suppression, and response to immunotherapy, and that lymphatic vessels negatively regulate T cells in tumors and thereby limit the persistence of T cell-mediated tumor control.
Therefore, Dr. Lund’s team is testing whether tumor-associated lymphatic vessels shape anti-tumor T cell responses and if they can be targeted to improve the effects of immunotherapy. This hypothesis will be tested through a variety of complementary approaches that explore three overarching concepts:
- that T cells exit tumors via lymphatic vessels and that novel inhibitors of T cell exit will have therapeutic potential;
- that lymphatic vessels present inhibitory molecules to negatively regulate T cell function and phenotype; and
- that lymphatic vessels select the information delivered to lymph nodes and thereby affect immune activation.
These interdisciplinary studies pair existing tools and models with a deep understanding of endothelial biology, tumor immunology, and melanoma, and should generate guiding principles to engineer lymphatic transport to improve immune activity against tumors. Additionally, they will use this new understanding to inform biomarker discovery and solidify an immunological framework for lymphatic vessels in melanoma. These principles together will point to novel lymphatic vessel-targeted strategies that expand patient responses to new and existing immunotherapies.
Projects and Grants
FasL Expressing Lymphatic Vessels
Oregon Health & Science University | Melanoma | 2015
Investigating and exploiting the lymphatic vasculature through the cancer immunity lifecycle
Oregon Health & Science University | Melanoma | 2019