University of Minnesota
MICaB Graduate Program
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Current Students

CNelson
Christine Nelson

E-mail:nels2264@umn.edu

Thesis Advisor: Vaiva Vezys

Year entered: 2012

Degrees received:
B.S., University of Minnesota, Minneapolis, MN 2007

Honors and Awards:

  • Honorable mention for NSF Graduate Research Fellowship Program
  • Immunology training grant; 2014, 2015
  • Dennis W. Watson Fellowship; 2015-2016
  • Doctoral Dissertation Fellowship; 2016-2017
  • Schmit-Steer Award University of Minnesota Medical Schoo;l 2016


Thesis Research:
T cell tolerance is a major barrier for effective cancer immunotherapy. While treatments, such as checkpoint blockade, have revitalized immunotherapy, it is unclear why only some patients have positive responses and what determines susceptibility to autoimmune-like adverse events. We utilized mice expressing defined self-antigens to uncover which CD8 T cell subsets respond to blockade therapy and how to manipulate unresponsive self-specific CD8 T cells. We show that activated, effector-like self-specific CD8 T cells respond to checkpoint blockade therapy, while anergic self-specific CD8 T cells are unresponsive to the effects of this therapy. We sought to determine ways to induce responsiveness in anergic or tolerant self-specific cells that were refractory to checkpoint blockade. In a model of peripheral tolerance to intestinal self-antigen, vaccination with vectors containing self-epitopes induced tolerance reversal and a proliferative program, which allowed CD8 T cells to respond to checkpoint blockade therapy. This suggested that T cell differentiation state is a critical factor in determining response to treatment. We also tested the ability of heterologous prime boost vaccination to induce responsiveness in endogenous, polyclonal self-antigen specific CD8 T cells. This vaccination platform induces similar responses in immune-competent mice expressing OVA as a self-antigen in the intestinal mucosa, as well as when melanocyte antigen is targeted in non-tg C57B/6 mice. These data expand our understanding of how the differentiation state of CD8 T cells affects the ability to respond to checkpoint blockade and how to modulate non-responsive self-specific CD8 T cell responses for therapeutic potential.

Publications:

  • Thompson, E.A., Beura, L.K., Nelson, C.E., Anderson, K.G., Vezys, V. 2016. Shortened Intervals during Heterologous Boosting Preserve Memory CD8 T Cell Function but Compromise Longevity. The Journal of Immunology 196: 3054-3063.
  • Pauken, K. E.*, Nelson, C. E.,* Martinov, T.*, Spanier, J. A., Heffernan, J. R., Sahli, N. L., et al. 2015. Cutting Edge: Identification of Autoreactive CD4+ and CD8+ T Cell Subsets Resistant to PD-1 Pathway Blockade. Journal of Immunology (Baltimore, Md. : 1950), 194(8), 3551–3555. *co-first author
  • Sowell, R. T., Rogozinska, M., Nelson, C. E., Vezys, V., & Marzo, A. L. 2014. Cutting Edge: Generation of Effector Cells That Localize to Mucosal Tissues and Form Resident Memory CD8 T Cells Is Controlled by mTOR. The Journal of Immunology, 193(5), 2067–2071.