4.5 Article

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

Journal

CELLULAR IMMUNOLOGY
Volume 366, Issue -, Pages -

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.cellimm.2021.104384

Keywords

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

Funding

  1. 'Tou Yan' Action of Heilongjiang province
  2. National Youth Talent Support Program of China [W03070060]
  3. National Natural Science Foundation of China [81871976, 81872435, U20A20377, 81672930]
  4. Excellent Youth Foundation of Heilongjiang Province [JQ2019H003]

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The combination therapy of STING agonist diABZI and IDO inhibitor 1-MT shows significant inhibition of tumor growth in CRC, leading to increased recruitment of immune cells and decreased infiltration of suppressor cells. This combination therapy holds promise as a potential option for the treatment of CRC.
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.

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