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

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/TAg(TNF-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/TAg(TNF-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/TAg(TNF-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.