LAUSR

Certain bacterial colonists induce a highly specific T cell response. A hallmark of this encounter is that adaptive immunity develops preemptively, in the absence of an infection. However, the functional properties of colonist-induced T cells are not well defined, limiting our ability to understand anticommensal immunity and harness it therapeutically. We addressed both challenges by engineering the skin bacterium Staphylococcus epidermidis to express tumor antigens anchored to secreted or cell-surface proteins. Upon colonization, engineered S. epidermidis elicits tumor-specific T cells that circulate, infiltrate local and metastatic lesions, and exert cytotoxic activity. Thus, the immune response to a skin colonist can promote cellular immunity at a distal site and can be redirected against a target of therapeutic interest by expressing a target-derived antigen in a commensal. Description Engineered bacteria as melanoma vaccine The skin microbiome usually lives in harmony with our tissues without inducing inflammation or mounting an infection. However, certain bacterial colonists, including the skin bacterium Staphylococcus epidermidis, can induce a highly specific adaptive immune response, the function of which is unclear. Chen et al. engineered an S. epidermidis strain to express melanoma tumor antigens and then tested their ability to drive antitumor immune responses (see the Perspective by Sajjath et al.). Engineered S. epidermidis generated tumor-specific T cells that infiltrated and reduced the growth of localized and metastatic melanoma. In combination with immune checkpoint inhibitors, these engineered skin bacteria caused mice to reject established tumors. These findings suggest that immune responses from engineered commensals may have therapeutic potential against other tumor antigens of interest. —PNK and STS A system to express tumor antigens in the skin commensal bacterium Staphylococcus epidermidis elicits T cells that treat local and systemic tumors.