TY - JOUR
T1 - In Situ Dendritic Cell Recruitment and T Cell Activation for Cancer Immunotherapy
AU - Han, Joonsu
AU - Bhatta, Rimsha
AU - Liu, Yusheng
AU - Bo, Yang
AU - Wang, Hua
N1 - Funding Information:
The authors would like to acknowledge the financial support from NSF DMR 2143673 (CAREER Award) and the start-up package from the Department of Materials Science and Engineering at the University of Illinois at Urbana-Champaign and the Cancer Center at Illinois.
Publisher Copyright:
Copyright © 2022 Han, Bhatta, Liu, Bo and Wang.
PY - 2022/8/23
Y1 - 2022/8/23
N2 - 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.
AB - 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.
KW - T cell
KW - cancer immunotherapy
KW - dendritic cell
KW - hydrogel
KW - solid tumor
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U2 - 10.3389/fphar.2022.954955
DO - 10.3389/fphar.2022.954955
M3 - Article
C2 - 36081933
AN - SCOPUS:85137999414
SN - 1663-9812
VL - 13
JO - Frontiers in Pharmacology
JF - Frontiers in Pharmacology
M1 - 954955
ER -