Roles of systemic immunity in tumor metastasis and effective immunotherapy
Nathan Reticker-Flynn, PhD
Assistant Professor of Otolaryngology - Head & Neck Surgery (OHNS)
OHNS/Head & Neck Surgery Divisions
Stanford University - Faculty
Friday, February 16, 2024
1:00 - 2:00pm (Please note the later time for this specific instance)
James H. Clark Center, Room S360, 3rd floor next to the Coffee Shop
Zoom link
Abstract
The majority of cancer-associated deaths result from distant organ metastases rather than primary tumors, yet few therapies exist to treat this stage of disease. Recent advances in tumor immunotherapies, such as immune checkpoint blockade, have shown promise for patients with metastatic disease, yet most patients remain unresponsive to these treatments.
Here, we investigate the roles of systemic immunity in metastatic progression and response to immunotherapies. We demonstrate that lymph node colonization plays a critical role in metastatic progression by imparting tumor-specific immune tolerance within the immune repertoire of the involved lymph nodes. This tolerance becomes systemic across the host and facilitates metastatic seeding of distant sites.
Furthermore, using mouse models and systems approaches, we demonstrate that the generation of effective anti-tumor immune responses to immunotherapies requires activation of immunity in secondary lymphoid organs. Together, these findings demonstrate the critical roles of lymph nodes in facilitating metastatic progression and driving responses to immunotherapy.
Bio
Nathan Reticker-Flynn is a tumor immunologist and Biomedical Engineer working at the interfaces of cancer metastasis, tumor evolution, adaptive immunity, and immunotherapy. He received his PhD from the Massachusetts Institute of Technology while working with Dr. Sangeeta Bhatia as part of the Harvard-MIT Division of Health Sciences and Technology. His doctoral studies focused upon developing screening platforms for interrogating interactions between tumors and extracellular matrix during metastatic progression and led to the discovery of aberrant glycosylation motifs that promote metastasis.
Dr. Reticker-Flynn performed his postdoctoral studies in the laboratory of Dr. Edgar Engleman at Stanford University School of Medicine. There, his work has focused on using systems approaches and mouse models to investigate tumor-immune interactions during metastasis and responses to immunotherapies. His discoveries include the revelation that effective immunotherapies require systemic activation of anti-tumor immunity and that lymph node metastases serve to reeducate adaptive immune responses in a manner that promotes distant metastasis.
Dr. Reticker-Flynn is currently an Assistant Professor at Stanford University in the Department of Otolaryngology and a member of the Stanford Cancer Institute. His lab uses systems approaches, combining patient samples and mouse models, to elucidate the mechanisms of tumor-immune tolerance during metastatic progression and develops novel immunotherapies that reverse tumor-specific tolerance to treat patients with metastatic disease.