Identifying baseline immune-related biomarkers to predict clinical outcome of immunotherapy.
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2017
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Abstract
As cancer strikes, individuals vary not only in terms of factors that contribute to its occurrence and development, but as importantly, in their capacity to respond to treatment. While exciting new therapeutic options that mobilize the immune system against cancer have led to breakthroughs for a variety of malignancies, success is limited to a subset of patients. Pre-existing immunological features of both the host and the tumor may contribute to how patients will eventually fare with immunotherapy. A broad understanding of baseline immunity, both in the periphery and in the tumor microenvironment, is needed in order to fully realize the potential of cancer immunotherapy. Such interrogation of the tumor, blood, and host immune parameters prior to treatment is expected to identify biomarkers predictive of clinical outcome as well as to elucidate why some patients fail to respond to immunotherapy. To approach these opportunities for progress, the Society for Immunotherapy of Cancer (SITC) reconvened the Immune Biomarkers Task Force. Comprised of an international multidisciplinary panel of experts, Working Group 4 sought to make recommendations that focus on the complexity of the tumor microenvironment, with its diversity of immune genes, proteins, cells, and pathways naturally present at baseline and in circulation, and novel tools to aid in such broad analyses.
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Gnjatic, Sacha, Vincenzo Bronte, Laura Rosa Brunet, Marcus O Butler, Mary L Disis, Jérôme Galon, Leif G Hakansson, Brent A Hanks, et al. (2017). Identifying baseline immune-related biomarkers to predict clinical outcome of immunotherapy. J Immunother Cancer, 5. p. 44. 10.1186/s40425-017-0243-4 Retrieved from https://hdl.handle.net/10161/16024.
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Brent A. Hanks
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:
- Investigating mechanisms of adaptive or acquired immunotherapy resistance in cancer
- Studying the relationship between EMT pathways and immunotherapy resistance.
- Elucidating mechanisms of dendritic cell tolerization in the tumor microenvironment and how these processes may contribute to immunotherapy resistance
- Development of novel pharmacologic and genetic strategies to overcome immunotherapy resistance
- Investigating mechanisms contributing to select immunotherapy-associated toxicities
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