AUTHOR=Han Joonsu , Bhatta Rimsha , Liu Yusheng , Bo Yang , Wang Hua TITLE=In Situ Dendritic Cell Recruitment and T Cell Activation for Cancer Immunotherapy JOURNAL=Frontiers in Pharmacology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.954955 DOI=10.3389/fphar.2022.954955 ISSN=1663-9812 ABSTRACT=

Cancer immunotherapy has shifted the paradigm for cancer treatment in the past decade, but new immunotherapies enabling the effective treatment of solid tumors are still greatly demanded. Here we report a pore-forming hydrogel-based immunotherapy that enables simultaneous recruitment of dendritic cells and in situ activation of T cells, for reshaping the immunosuppressive tumor microenvironment and amplifying cytotoxic T lymphocyte response. The injectable pore-forming hydrogel composed of porogen-dispersed alginate network can form a macroporous structure upon injection into mice, and enables controlled release of granulocyte-macrophage colony-stimulating factor (GM-CSF), a chemoattractant for recruiting dendritic cells, and epacadostat, an inhibitor of indoleamine 2, 3-dioxygenase for activating T cells. We show that gels loaded with GM-CSF and epacadostat, after peritumoral injection, can recruit massive dendritic cells in situ and activate effector T cells in the tumor tissues, resulting in enhanced frequency and activation status of dendritic cells, reduced numbers of regulatory T (Treg) cells, and increased CD8+/Treg ratios in the tumor microenvironment. This hydrogel-based immunotherapy holds great promise for treating poorly-immunogenic solid tumors.