alpha-toxin inhibits CD8 T cell-mediated killing of cancer cells in cutaneous T-cell lymphoma.

and its toxins have been linked to disease progression and mortality in advanced stages of cutaneous T-cell lymphoma (CTCL). CD8 T cells play a crucial role in anti-cancer responses and high CD8 T cell numbers in tumor lesions are associated with a favorable prognosis in CTCL. Here, we show that CD8 T cells from both healthy donors and Sézary syndrome patients are highly susceptible to cell death induced by Staphylococcal alpha-toxin, whereas malignant T cells are not. Importantly, alpha-toxin almost completely blocks cytotoxic killing of CTCL tumor cells by peptide-specific CD8 T cells, leading to their escape from induced cell death and continued proliferation. These findings suggest that alpha-toxin may favor the persistence of malignant CTCL cells by inhibiting CD8 T cell cytotoxicity. Thus, we propose a novel mechanism by which colonization with may contribute to cancer immune evasion and disease progression in CTCL.