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

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

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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