Novel Adjuvants

Temizoz, Burcu; Kuroda, Etsushi; Kobiyama, Kouji; Aoshi, Taiki; Ishii, Ken J.

doi:10.1007/978-4-431-55031-0_17

Cited by 1 publication

(1 citation statement)

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Despite extensive research and recent improvements in prognosis, prevention, and treatment, cancer is a leading cause of death worldwide. Colon carcinoma is the third most prevalent cancer and the second most lethal cancer in the world (1)(2)(3).…”

Section: Introductionmentioning

confidence: 99%

Immunotherapy with STING and TLR9 agonists promotes synergistic therapeutic efficacy with suppressed cancer-associated fibroblasts in colon carcinoma

Hajiabadi,

Alidadi,

Montakhab Farahi

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

The innate immune sensing of nucleic acids using effective immunoadjuvants is critical for increasing protective immune responses against cancer. Stimulators of interferon genes (STING) and toll-like receptor 9 (TLR9) agonists are considered promising candidates in several preclinical tumor models with the potential to be used in clinical settings. However, the effects of such treatment on tumor stroma are currently unknown. In this study, we investigated the immunotherapeutic effects of ADU-S100 as a STING agonist and CpG ODN1826 as a TLR9 agonist in a preclinical model of colon carcinoma. Tumor-bearing mice were treated intratumorally on days 10 and 16 post-tumor inoculation with ADU-S100 and CpG ODN1826. Cytokine profiles in the tumor and spleen, tumor cell apoptosis, the infiltration of immune cells, and cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) were evaluated to identify the immunological mechanisms after treatment. The powerful antitumor activity of single and combination treatments, the upregulation of the expression of pro-inflammatory cytokines in the tumor and spleen, and the recruitment and infiltration of the TME by immune cells revealed the synergism of immunoadjuvants in the eradication of the colon carcinoma model. Remarkably, the significant downregulation of CAFs in the TME indicated that suppression of tumorigenesis occurred after immunoadjuvant therapy. The results illustrate the potential of targeting the STING and TLR9 pathways as powerful immunoadjuvants in the treatment of preclinical colon carcinoma and the possibility of harnessing these pathways in future therapeutic approaches.

show abstract

Section: Introductionmentioning

confidence: 99%