Anti-tumor effects in head and neck cancer in response to toll-like receptor activation, checkpoint inhibition, and chemotherapy

Head and neck cancer (HNC) affects approximately 600,000 individuals annually and occurs when squamous cells lining the oral cavity, nasal cavity, and throat become cancerous. Certain problems are associated with current therapies. Surgery can lead to a lower quality of life due to functional and cosmetic disturbances while chemotherapy and radiation have high toxicity levels. In addition, chemotherapy has low response rates and high recurrence rates. Thus, it is necessary to utilize immune-directed therapies to treat patients in a process called cancer immunotherapy.In this study, the therapeutic efficacy of combination cancer immunotherapy is studied on murine models inoculated with squamous cell carcinoma VII. The hypothesis is that using a combination of immunotherapeutic methods and standard treatment can lead to smaller sizes of local, distant, and subsequent tumors. In this study, the immune system is activated and enhanced through the activation of toll-like receptors (TLRs) and the inhibition of immune checkpoints. Treatment methods including TLR7 activation with a 1V270 ligand, TLR9 activation with a SD-101 ligand, checkpoint inhibition with an anti-PD-1 monoclonal antibody, chemotherapy drug, cisplatin, and combination approaches were tested. When used in conjunction with anti-PD-1 agent, 1V270 and SD-101 both showed a reduction in growth on local, distant, and subsequent tumors. 1V270 with cisplatin showed a reduction in growth on local and subsequent tumors. Upon further investigation of the infiltrating cells in the tumor microenvironment by FACS, the combination therapy of 1V270 with cisplatin or anti-PD-1 agent provided higher anti-tumor M1 macrophage to pro-tumorigenic M2 macrophage ratio