Immune evasion pathways and the design of dendritic cell-based cancer vaccines.

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2016-02

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Abstract

Emerging data is suggesting that the process of dendritic cell (DC) tolerization is an important step in tumorigenesis. Our understanding of the networks within the tumor microenvironment that functionally tolerize DC function is evolving while methods for genetically manipulating DC populations in situ continue to develop. A more intimate understanding of the paracrine signaling pathways which mediate immune evasion by subverting DC function promises to provide novel strategies for improving the clinical efficacy of DC-based cancer vaccines. This will likely require a better understanding of both the antigen expression profile and the immune evasion network of the tumor and its associated stromal tissues.

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Hanks

Brent A. Hanks

Associate Professor of Medicine

We are interested in understanding the mechanisms that cancers have evolved to suppress the generation of tumor antigen-specific immune responses and how this knowledge can be exploited for the development of novel and more effective cancer immunotherapy strategies. This work involves the utilization of both autochthonous transgenic tumor model systems as well as clinical specimens to develop novel strategies to enhance the efficacy of immunotherapies while also developing predictive biomarkers to better guide the management of cancer patients with these agents. We strive to translate our understanding of the fundamental biochemical and metabolic pathways within the tumor microenvironment that are critical for driving immune evasion and resistance into early phase clinical trial testing.

Our work utilizes a variety of techniques and methodologies that span the breadth of basic biological research. This work integrates studies based on both 1) transgenic mouse tumor models that are monitored using bioluminescence and micro-CT imaging and 2) a variety of clinical specimens.

Our current areas of focus include:

  1. Investigating mechanisms of adaptive or acquired immunotherapy resistance in cancer
  2. Studying the relationship between EMT pathways and immunotherapy resistance.
  3. Elucidating mechanisms of dendritic cell tolerization in the tumor microenvironment and how these processes may contribute to immunotherapy resistance
  4. Development of novel pharmacologic and genetic strategies to overcome immunotherapy resistance
  5. Investigating mechanisms contributing to select immunotherapy-associated toxicities

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