The tumor microenvironment generated by Marek's disease virus suppresses interferon-gamma-producing gamma delta T cells

The tumor microenvironment (TME) is generated by the cross-talk among tumor cells, immune system cells, and stromal cells. The TME generated by Marek's disease virus (MDV) is suggested to display an immunosuppressive milieu due to immune inhibitory molecules and cytokines which are possibly induced by MDV-transformed cells and regulatory T cells. Both anti-tumor and pro-tumor gamma delta (gamma delta) T cells are reported in human cancer. Although anti-tumor like and pro-tumor like gamma delta T cells are found in MDV-infected chickens at the later phase of infection, how the TME affects circulating and tissue-resident gamma delta T cells has not been investigated. Here, we demonstrated that the supernatant of the cultured splenocytes derived from MDV-challenegd chickens inhibited interferon (IFN)-gamma production and CD25 expression by T cell receptor (TCR)gamma delta-stimulated tissue-resident gamma delta T cells, but the supernatant of the cultured MDV-transformed cell line did not affect gamma delta T cell activation. TCR gamma delta stimulated circulating gamma delta T cells were influenced neither by the supernatant of the cultured splenocytes derived from MDV-challenegd chickens nor by the supernatant of the cultured MDV-transformed cell line. Taken together, activation and IFN-gamma production by tissue-resident gamma delta T cells can be inhibited in the TME generated by MDV while tumor attracted circulating gamma delta T cells may not be influenced in activation and IFN-gamma production by the TME generated by MDV.