Ameliorating the tumor microenvironment for antitumor responses through TLR5 ligand-secreting T cells.

Toll-like receptor (TLR) agonists are potent immunostimulatory agents that have demonstrated great potential for cancer immunotherapy. We have genetically-engineered tumor-specific T cells to deliver and secrete the TLR5 ligand (TLR5L) flagellin to the tumor site to provide costimulation for antitumor immune activity. We found that TLR5L-secreting T cells offered a therapeutic benefit by altering several aspects including augmenting T cell effector function and expansion as well as reshaping the tumor microenvironment toward one that enhances antitumor T cell responses.