Open Access

Treatment with cyclophosphamide supported by various dendritic cell-based vaccines induces diversification in CD4+ T cell response against MC38 colon carcinoma

  • Authors:
    • Justyna Wojas-Turek
    • Agnieszka Szczygieł
    • Jagoda Kicielińska
    • Joanna Rossowska
    • Egbert Piasecki
    • Elżbieta Pajtasz-Piasecka
  • View Affiliations

  • Published online on: December 7, 2015     https://doi.org/10.3892/ijo.2015.3278
  • Pages: 493-505
  • Copyright: © Wojas-Turek et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study shows that an application of cyclophosphamide (CY) supported by dendritic cell (DC)-based vaccines affected differentiation of the activity of CD4+ T cell subpopulations accompanied by an alteration in CD8+ cell number. Vaccines were composed of bone marrow-derived DCs activated with tumor cell lysate (BM-DC/TAgTNF-α) and/or genetically modified DCs of JAWS II line (JAWS II/Neo or JAWS II/IL-2 cells). Compared to untreated or CY-treated mice, the combined treatment of MC38 colon carcinoma-bearing mice resulted in significant tumor growth inhibition associated with an increase in influx of CD4+ and CD8+ T cells into tumor tissue. Whereas, the division of these cell population in spleen was not observed. Depending on the nature of DC-based vaccines and number of their applications, both tumor infiltrating cells and spleen cells were able to produce various amount of IFN-γ, IL-4 and IL-10 after mitogenic ex vivo stimulation. The administration of CY followed by BM-DC/TAgTNF-α and genetically modified JAWS II cells, increased the percentage of CD4+T-bet+ and CD4+GATA3+ cells and decreased the percentage of CD4+RORγt+ and CD4+FoxP3+ lymphocytes. However, the most intensive response against tumor was noted after the ternary treatment with CY + BM-DC/TAgTNF-α + JAWS II/IL-2 cells. Thus, the administration of various DC-based vaccines was responsible for generation of the diversified antitumor response. These findings demonstrate that the determination of the size of particular CD4+ T cell subpopulations may become a prognostic factor and be the basis for future development of anticancer therapy.

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Copy and paste a formatted citation
APA
Wojas-Turek, J., Szczygieł, A., Kicielińska, J., Rossowska, J., Piasecki, E., & Pajtasz-Piasecka, E. (2016). Treatment with cyclophosphamide supported by various dendritic cell-based vaccines induces diversification in CD4+ T cell response against MC38 colon carcinoma. International Journal of Oncology, 48, 493-505. https://doi.org/10.3892/ijo.2015.3278
MLA
Wojas-Turek, J., Szczygieł, A., Kicielińska, J., Rossowska, J., Piasecki, E., Pajtasz-Piasecka, E."Treatment with cyclophosphamide supported by various dendritic cell-based vaccines induces diversification in CD4+ T cell response against MC38 colon carcinoma". International Journal of Oncology 48.2 (2016): 493-505.
Chicago
Wojas-Turek, J., Szczygieł, A., Kicielińska, J., Rossowska, J., Piasecki, E., Pajtasz-Piasecka, E."Treatment with cyclophosphamide supported by various dendritic cell-based vaccines induces diversification in CD4+ T cell response against MC38 colon carcinoma". International Journal of Oncology 48, no. 2 (2016): 493-505. https://doi.org/10.3892/ijo.2015.3278