Date of Award

January 2019

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Marcus Bosenberg

Abstract

Metastatic melanoma historically carries a grim prognosis, with a median survival of 9 months and a long-term survival rate of 10%. Melanoma is highly immunogenic, and the development of immunotherapies has dramatically changed the landscape of metastatic melanoma treatment. To study the immune mechanisms engaged by these therapies, the Bosenberg lab developed YUMMER, an immunogenic mouse melanoma line that forms tumors when injected into mice. This and other immunogenic murine cancer models were used to demonstrate that B cell depletion does not impair the anti-PD-1-induced anti-tumor immune response in mice. In addition, supplementing immune checkpoint inhibition with therapies targeting myeloid cells increases the efficacy of immune checkpoint inhibitors and can convert resistant tumors into sensitive tumors. Last, a novel model was developed that allows for comparison of failed and successful anti-tumor immune responses, and we propose how it may be employed to study the role of T cell dysfunction in immune checkpoint inhibitor resistance.

Comments

This thesis is restricted to Yale network users only. It will be made publicly available on 07/15/2021

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