Head and neck cancers have been reported to have high immune infiltration scores, and clinical benefits of the anti-PD1 checkpoint inhibitor have been demonstrated in recurrent and metastatic cancers. Recent genetic signa-tures of the immune compartment have provided insights to delineate immune-active and -exhausted subtypes, to understand the immune status of OSCC patients that could further drive the development of novel immunotherapies. Vaccination with tumour-associated antigens is an approach to improve tumour recognition which could result in the eradication of cancer cells. Here, I would describe our efforts in developing antigen-specific vaccines for head and neck cancer. Using the B6.Cg-Tg(HLA-A/H2-D)2Enge/J mice bearing established tumours overexpressing the tumour antigens, we demonstrated that the vaccine delayed tumour growth, and in combination with anti-PD1, completely eliminated the tumour. The vaccine increased the expression of PD1 in T cells, and vaccinated animals showed increased antigen-specific responses by the ELISPOT assay. In summary, our data show that antigen-specific vaccine works synergistically with anti-PD1 and could be a promising therapeutic agent for head and neck cancer.