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

  • Cell Immunol. 2021 Aug:366:104384. doi: 10.1016/j.cellimm.2021.104384.
Jiaqi Shi  1 ,  Caiqi Liu  1 ,  Shengnan Luo  2 ,  Tingyu Cao  3 ,  Binlin Lin  3 ,  Meng Zhou  4 ,  Xiao Zhang  5 ,  Song Wang  5 ,  Tongsen Zheng  6 ,  Xiaobo Li  7
Affiliations
  • 1. Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, No. 150 Haping Road, Nangang District, Harbin 150081, PR China; Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin 150081, PR China; Heilongjiang Key Laboratory of Molecular Oncology, No. 150 Haping Road, Nangang District, Harbin 150081, PR China.
  • 2. Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, No. 150 Haping Road, Nangang District, Harbin 150081, PR China; Heilongjiang Key Laboratory of Molecular Oncology, No. 150 Haping Road, Nangang District, Harbin 150081, PR China.
  • 3. Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, No. 150 Haping Road, Nangang District, Harbin 150081, PR China.
  • 4. Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, No. 150 Haping Road, Nangang District, Harbin 150081, PR China; Heilongjiang Cancer Institute, No. 150 Haping Road, Nangang District, Harbin 150081, PR China.
  • 5. Department of Pathology, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150081, PR China.
  • 6. Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, No. 150 Haping Road, Nangang District, Harbin 150081, PR China; Heilongjiang Key Laboratory of Molecular Oncology, No. 150 Haping Road, Nangang District, Harbin 150081, PR China; Department of Phase 1 Trials Center, Harbin Medical University Cancer Hospital, No. 150 Haping Road, Nangang District, Harbin 150081, PR China. Electronic address: [email protected].
  • 7. Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin 150081, PR China; Department of Pathology, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150081, PR China. Electronic address: [email protected].
PMID: 34182334 DOI: 10.1016/j.cellimm.2021.104384
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.

Keywords
3 Dioxygenase (IDO); Colorectal cancer (CRC); Combination immunotherapy; Indoleamine 2; PD-1 blockade; Stimulator of interferon genes (STING).
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