Vdelta1 T cells are more resistant than Vdelta2 T cells to the immunosuppressive properties of galectin-3

Ovarian carcinomas have the highest lethality amongst gynecological tumors. A problem after primary resection is the recurrence of epithelial ovarian carcinomas which is often associated with chemotherapy resistance. To improve the clinical outcome, it is of high interest to consider alternative therapy strategies. Due to their pronounced plasticity, gamma delta T cells are attractive for T-cell-based immunotherapy. However, tumors might escape by the release of lectin galectin-3, which impairs gamma delta T-cell function. Hence, we tested the effect of galectin-3 on the different gamma delta T-cell subsets. After coculture between ovarian tumor cells and V delta 1 or V delta 2 T cells enhanced levels of galectin-3 were released. This protein did not affect the cytotoxicity of both gamma delta T-cell subsets, but differentially influenced the proliferation of the two gamma delta T-cell subsets. While increased galectin-3 levels and recombinant galectin-3 inhibited the proliferation of V delta 2 T cells, V delta 1 T cells were unaffected. In contrast to V delta 1 T cells, the V delta 2 T cells strongly upregulated the galectin-3 binding partner alpha 3 beta 1-integrin after their activation correlating with the immunosuppressive properties of galectin-3. In addition, galectin-3 reduced the effector memory compartment of zoledronate-activated V delta 2 T cells. Therefore, our data suggest that an activation of V delta 1 T-cell proliferation as part of a T-cell-based immunotherapy can be of advantage.