Simplified schematic showing the proposed mechanism of how SEs may suppress cellular immunity and antitumor responses. (A) In contrast to benign T cells, malignant T cells typically express a monoclonal TCR Vβ chain and often exhibit decreased expression or function of the TCR complex. SEs may therefore in many cases not stimulate malignant T cells directly but rather indirectly through activation of benign T cells. (B) Upon colonization with enterotoxin-producing SA bacteria, SEs bind MHC-II molecules expressed on malignant T cells, benign T cells, and antigen-presenting cells. SEs bound to MHC-II molecules subsequently crosslink TCRs on benign T cells, which elicits cell-cell contact–dependent interactions between the benign and malignant T cells and triggers secretion of IL-2 from the benign T cells. (C) These signals in turn induce high expression of IL-10 from the malignant T cells via a Jak3/Stat3-dependent pathway. IL-10 secreted from the malignant T cells can dampen cellular immunity by several means. For example, IL-10 impairs the maturation of dendritic cells, represses the expression of Th1 cytokines (interferon-γ, IL-12), inhibits T-cell activation, and promotes the function of regulatory T cells as well as the development of immunoregulatory M2 macrophages (MΦ), collectively contributing to suppression of cellular immunity and antitumor immune responses. The malignant T cells, however, display deficient expression of IL-10R and are therefore protected against the suppressive effects of IL-10. DC, dendritic cell; IFN-γ, interferon-γ.