Many studies have shown persistent activation of STAT3 in myeloid cells and T cells at primary tumor sites, leading to an immunosuppressive environment which allows for tumor angiogenesis, growth and metastasis [114] More specifically, STAT3 mediated immunosuppression has been linked to its function downstream of cytokines and T cell inhibitory or “checkpoint” molecules, such as IL-27, PDL-1 and HVEM that promote the differentiation of regulatory T cell subsets [115,116,117,118]. This evidence concerns the gene TNFRSF14 and neoplasm.