| dc.description.abstract | Head and neck squamous cell carcinoma (HNSCC) constitute a group of tumors originating from mucosal epithelium in the oral cavity, pharynx, larynx, nasal cavity, and salivary glands. Globally, it ranks as the sixth most common cancer, highlighting the pressing need for the development of new therapies to enhance recovery and survival rates in patients. Activation of pattern recognition receptors (PRRs) initiates innate immune responses, subsequently triggering adaptive immune responses. Given their potent immune stimulatory properties that aid in the eradication of cancer cells, various PRR agonists are being investigated for cancer immune therapies. To investigate the immune mechanism and antitumor function in vivo, we utilized an orthotopic syngeneic head and neck cancer mouse model. We investigated the immune response and antitumor activities of TLR9 agonist and STING agonists, both individually and in combination. In splenocytes, bone marrow-derived macrophages (BMDMs) and bone marrow-derived dendritic cells (BMDCs), CpG-2722 showed increased expression of Th1 and Th17 cytokines but not Th2 cytokines. STING agonists exhibited lower expression of Th1 and Th17 but higher expression of Th2 cytokines compared to CpG-2722. However, the combination of CpG-2722 with each STING agonist significantly enhanced Th1 and Th17 cytokine expressions while reducing Th2 cytokine expressions. CpG-2722 and 2’3’-c-di-AMP effectively induced cellular immune responses, including upregulation of IFN-γ, TNF-α, IL-1β, IL-6, and IL-23A cytokines expression, as well as maturation markers CD86, CD80, CD40, and CCR7 in DCs. Their combination demonstrated cooperative activity in vitro. Both CpG-2722 and 2’3’-c-di-AMP suppressed head and neck tumor growth, with their combination proving more effective than using these agonists alone. In the tumor microenvironment, the combined treatment of CpG-2722 and 2’3’-c-di-AMP cooperatively promoted the production of IFN-γ, IL-12, IL-1β, and type I IFN cytokines. Additionally, it led to the accumulation of leukocytes, CD4, and CD8 T cells, maturation of cDCs and pDCs, and reprogramming of tumor-associated macrophages into M1 macrophages. Thus, this finding indicates the potent cancer immunotherapy agent through the cooperative activation of TLR9 and STING agonists in head and neck cancer. | en_US |