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Expansion of melanoma-specific lymphocytes in alternate gamma chain cytokines: gene expression variances between T cells and T-cell subsets exposed to IL-2 versus IL-7/15

Cancer Gene Therapy volume 21, pages 441–447 (2014)Cite this article

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Abstract

We have previously demonstrated that expansion of activated tumor-sensitized T cells in interleukin (IL)-7/15 results in greater expansion and antitumor activity than expansion in IL-2. We sought to determine whether T cells exposed to IL-2 versus IL-7/15 exhibited distinct gene expression patterns. Lymphocytes were harvested from Pmel-1 mice immunized with B16-GMCSF melanoma cells, activated in vitro, and cultured in IL-2 or IL-7/15 for 1, 3 or 6 days. T cells were harvested and analyzed using microarray, real-time quantitative polymerase chain reaction (RT-QPCR) or sorted into T-cell subsets and analyzed. We found significant differences in gene expression for T cells cultured in IL-2 versus IL-7/15, starting on day 3. This was not a function of subset differentiation; when T cells were divided into subsets, the central memory (TCM), effector memory (TEM) and effector (TE) T cells cultured in the IL-2 more closely resembled each other than the identical phenotypic subset exposed to IL-7/15. Thus, the differences in gene expression induced by culture in IL-2 versus IL-7/15 do not merely reflect differences in the frequency of TCM versus TEM versus TE cells, but rather reflect that the gene expression levels of those T-cell subsets when exposed to different cytokines are fundamentally different.

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Acknowledgements

We gratefully acknowledge the support of VCU Massey Cancer Center, the Women and Wellness Fund and the VCU Massey Cancer Center Flow Cytometry Shared Resource, supported, in part, with funding from NIH-NCI Cancer Center Support Grant P30 CA016059.

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Authors and Affiliations

  1. Department of Surgery, Virginia Commonwealth University Health System, Richmond, VA, USA

    C K Zoon & H D Bear

  2. Division of Surgical Oncology, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, USA

    E Seitelman, L Graham & H D Bear

  3. Department of Microbiology and Immunology, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, USA

    S Keller

  4. Department of Pathology, Virginia Commonwealth University Health System, Richmond, VA, USA

    T L Blevins & C I Dumur

Authors
  1. C K Zoon
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  2. E Seitelman
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  6. C I Dumur
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  7. H D Bear
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Correspondence to C K Zoon.

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Zoon, C., Seitelman, E., Keller, S. et al. Expansion of melanoma-specific lymphocytes in alternate gamma chain cytokines: gene expression variances between T cells and T-cell subsets exposed to IL-2 versus IL-7/15. Cancer Gene Ther 21, 441–447 (2014). https://doi.org/10.1038/cgt.2014.48

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  • DOI: https://doi.org/10.1038/cgt.2014.48

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