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  • Open Access

IL-12 primed CD8+ T-cells possess enhanced persistence and anti-tumor efficacy because of greater IL-7 responsiveness

  • 1,
  • 1,
  • 1,
  • 1 and
  • 1
Journal for ImmunoTherapy of Cancer20131 (Suppl 1) :P17

https://doi.org/10.1186/2051-1426-1-S1-P17

  • Published:

Keywords

  • Irradiate Mouse
  • Effector Phase
  • Great Expansion
  • Molecule STAT5
  • Adoptive Cell Transfer

Ex vivo IL-12 priming of tumor-reactive CD8+ T-cells enhances their persistence and subsequent anti-tumor efficacy upon adoptive cell transfer (ACT) into lymphodepleted mice. Since IL-7 and IL-15 are considered critical for the persistence of adoptively transferred T-cells, we investigated the responsiveness of IL-12 primed CD8+ T-cells to these homeostatic cytokines to help elucidate the mechanisms behind their superior anti-tumor abilities. Using pmel-1 T-cell receptor transgenic mice, we found that pmel CD8+ T cells activated in the presence of IL-12 (pmelIL-12) showed much greater expansion in an irradiated (6 Gy) host compared to cells activated without IL-12 (pmelsham). This expansion was dependent on host IL-7, but not IL-15. Compared to pmelsham, pmelIL-12 demonstrated greatly enhanced in vitro IL-7 responsiveness, as measured by proliferation and phosphorylation of signaling molecules STAT5, S6 and AKT. These striking differences were not seen with IL-15. Despite not playing a major role in pmelIL-12 effector phase expansion, IL-15 was critical for maximum anti-tumor efficacy of pmelIL-12, as irradiated mice devoid of IL-15, like mice receiving IL-7 neutralizing antibody (clone M25), showed reduced survival compared to irradiated mice receiving pmelIL-12 only. This decreased tumor control likely occurred because IL-15 was needed for long-term persistence of pmelIL-12. Together, these findings suggest that IL-12 priming of CD8+ T-cells augments the efficacy of ACT protocols in part by conferring an enhanced ability to respond to IL-7, thereby enabling transferred cells to persist in the IL-7 rich post-lymphodepletion environment.

Authors’ Affiliations

(1)
Medical University of South Carolina, Charleston, SC, USA

Copyright

© Johnson et al; licensee BioMed Central Ltd. 2013

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/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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