STING agonist and IDO inhibitor combination therapy inhibits tumor progression in murine models of colorectal cancer.

Abstract

Despite impressive clinical success, cancer immunotherapy based on immune checkpoint blockade remains ineffective in colorectal cancer (CRC). Stimulator of interferon genes (STING) is a novel potential target and STING agonists have shown potential anti-tumor efficacy. Combined therapy based on synergistic mechanism can overcome the resistance. However, STING agonists-based combination therapies are deficient. We designed different immunotherapy combinations, including STING agonist, indoleamine 2,3 dioxygenase (IDO) inhibitor and PD-1 blockade, with purpose of exploring which option can effectively inhibit CRC growth. To further explore the possible reasons of therapeutic effectiveness, we observed the combination therapy in C57BL/6Tmem173gt mice. Our findings demonstrated that STING agonist diABZI combined with IDO inhibitor 1-MT significantly inhibited tumor growth, even better than the three-drug combination, promoted the recruitment of CD8+ T cells and dendritic cells, and decreased the infiltration of myeloid-derived suppressor cells. We conclude that diABZI combined with 1-MT is a promising option for CRC.

• Authors: Jiaqi Shi, Caiqi Liu, Shengnan Luo, Tingyu Cao, Binlin Lin, Meng Zhou, Xiao Zhang, Song Wang, Tongsen Zheng, Xiaobo Li
• Journal: Cellular immunology (Cell Immunol) Vol. 366 Pg. 104384 (08 2021) ISSN: 1090-2163 [Electronic] Netherlands
• PMID: 34182334 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• 1-methyl-L-tryptophan
• Benzimidazoles
• Immune Checkpoint Inhibitors
• Indoleamine-Pyrrole 2,3,-Dioxygenase
• Membrane Proteins
• Pdcd1 protein, mouse
• Programmed Cell Death 1 Receptor
• Sting1 protein, mouse
• Tryptophan

Topics

• Adenocarcinoma (drug therapy)
• Animals
• Antineoplastic Combined Chemotherapy Protocols (pharmacology, therapeutic use)
• Benzimidazoles (pharmacology, therapeutic use)
• CD8-Positive T-Lymphocytes (immunology)
• Carcinogenesis
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Colorectal Neoplasms (drug therapy)
• Disease Models, Animal
• Disease Progression
• Female
• Humans
• Immune Checkpoint Inhibitors (therapeutic use)
• Immunotherapy (methods)
• Indoleamine-Pyrrole 2,3,-Dioxygenase (antagonists & inhibitors)
• Membrane Proteins (agonists)
• Mice
• Mice, Inbred C57BL
• Myeloid-Derived Suppressor Cells (immunology)
• Neoplasm Transplantation
• Programmed Cell Death 1 Receptor (antagonists & inhibitors)
• Tryptophan (pharmacology, therapeutic use)