Immunological Homeostasis and Melanoma
Funding:
Department of Veterans Affairs - Career Development Award (CDA-2)
Principal Investigator:
Project Summary:
Surgical therapy has emerged as the mainstay of treatment for melanoma. Unfortunately, for patients with disease not amenable to surgical resection, effective oncological care is limited by the absence of effective systemic treatment options. Great effort has been directed toward the development of anti-melanoma immunotherapies, which take advantage of the fascinating ability of the immune system to (1) respond to a nearly limitless spectrum of foreign agents and (2) “remember” those agents against future encounters (so-called immunological memory). To date, attempts to orient the immune system to recognize, eliminate, and remember melanoma cells have been largely unsuccessful. It is theorized that an ability of melanoma to circumvent the immune system may be responsible for this clinical failure.
The overall hypothesis of our research effort is that growing melanoma tumors exert an active suppressive influence on the ability of immune cells to become fully activated to mount effective immune reactions and establish immunological memory. The existence of such an influence would clearly explain the failure of experimental immunotherapies to effectively treat melanoma. We have recently developed a novel experimental animal model that not only confirms but also quantifies the ability of growing melanoma tumors to suppress the strength of acute immune responsiveness. In this proposal, we have outlined a plan to use this unique experimental system to answer fundamental questions about the impact of melanoma on the immune system. Specifically, we will work to identify basic cellular mechanisms underlying the immunosuppressive influence of melanoma. We will also modify this model to quantify the influence of melanoma on immunological memory. Finally, we will use the model to test the ability of immunomodulatory strategies to block the immunosuppressive influence of melanoma.
By elucidating the nature and the mechanisms underlying melanoma-induced immune suppression, the ultimate goal of my research effort is to identify strategies with which this clinically undesirable phenomenon may be blocked. A discovery of this nature could allow us to finally realize the enormous but as yet theoretical potential of anti-cancer immunotherapy - which would offer patients with melanoma a desperately needed strategy of systemic treatment that currently does not exist.
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General Surgery
University of Wisconsin Department of Surgery
First published: 07/15/02 Last updated: 11/24/09 webmaster@surgery.wisc.edu
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