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  • Open Access

Wnt pathway activation functionally reprograms human antigen-specific T cells

  • 1,
  • 2,
  • 3,
  • 4 and
  • 4
Journal for ImmunoTherapy of Cancer20142(Suppl 3):P4

https://doi.org/10.1186/2051-1426-2-S3-P4

Published: 6 November 2014

Keywords

  • Effector Function
  • Protective Immunity
  • Human Memory
  • Cancer Antigen
  • Adoptive Immunotherapy

Polyfunctionality is a hallmark of protective immunity, yet the molecular mechanisms governing polyfunctional T cells are poorly understood. After TCR activation, naïve CD8+ T cells undergo proliferation and differentiation, which lead to effector functions and memory subset development. However only a portion of activated T cells develop into memory CD8+ T cells and with chronic stimulation become terminally differentiated and exhausted CD8+ T cells, as defined by CCR7-/CD45RA+, and functionally impair effective immune responses [1]. We therefore probed the ability to reverse terminally differentiated antigen-specific cells using pharmacological agents. Stimulating human memory CD8+ T cells with cognate TCR stimulation in the presence of Wnt agonist enhances polyfunctionality and stemness. Both M1-influenza+ and CMV+ CD8+ T cell responses were reprogrammed and revealed sustained effects from initial Wnt pathway activation in vitro. Future work with cancer antigens and reprogramming of differentiated CD8+ responses could lead to improved in vitro culture conditions for adoptive immunotherapy.

Authors’ Affiliations

(1)
Department of Medicine, Far-Eastern Memorial Hospital, New Taipei City, Taiwan
(2)
Department of Pathology Johns Hopkins University School of Medicine, Baltimore, USA
(3)
Department of Medicine, and Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, USA
(4)
Johns Hopkins School of Medicine, Department of Pathology, Institute for Cell Engineering, Baltimore, USA

References

  1. Seder R, Darrah P, Roederer M: T-cell quality in memory and protection: implications for vaccine design. Nat Rev Immunol. 2008, 8: 247-258. 10.1038/nri2274.View ArticlePubMedGoogle Scholar

Copyright

© Chiu et al.; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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