Project Summary Deaths from solid tumors vastly outnumber deaths from hematopoietic cancers. Yet progress in immunotherapies for solid tumors is well behind those for lymphoma. CAR-T cell therapies and engineered T cells have become revolutionary approaches for hematopoietic cancers, but their potential for solid tumors is yet to be realized. Significant challenges hinder the potential of immune therapies in solid tumors, including insufficient activation and eventual exhaustion of effector T cells; and suppression of T cell effector responses in the tumor microenvironment. In this proposal we consider these hurdles and offer a biomaterial solution that overcomes them. This proposal is significant in facilitating endogenous T cells to fight solid tumors. Surgery is a major treatment modality for both invasive and in situ tumors, but at this time, there are no specific immunotherapies initiated at the time of surgery; they all start days to weeks later. Our proposal is significant for offering a way to start treatments early, right at the time of initial surgery. Here our synthetic scaffold, SymphNode can be injected at the time of biopsy or surgery not to only recruit and active tumor-experienced local immune cells but also to suppress the inhibitory cells created by tumor cells. Our long-term goal is to develop this bioengineered, locally injected, “synthetic lymph node” into a therapy for human tumors.