Bacteria-based immunotherapies against cancer

Conventional CD4+ T cells contribute to early immune responses by capturing bacteria by transphagocytosis. Surprisingly, transphagocytic CD4+ T cells destroy internalized bacteria. Exposure to bacteria “trains” CD4+ T cells that overexpress MHC-I and coestimulatory molecules and become hyperinflammatory secreting locally inflammatory cytokines that could block the immunosuppressive environment generated by solid tumor. Moreover, bacteria-trained (tr) CD4+ T cells differentiate into antigen cross-presenting cells, potently activating naïve CD8+ T cells, and generate central memory CD8+ T cells expressing very low levels of PD-1. These activities are all involved in the removal of tumors. Together, these effects prompted us to hypothesized that trCD4+ T cells could be useful in antitumor therapies. This hypothesis was tested in a proof-of-concept model of aggressive mouse melanoma, and now it is in our aim to test it in other tumor models.