Therapeutic Vaccination in Head and Neck Squamous Cell Carcinoma—A Review

Abstract

Therapeutic vaccination is one of the most effective immunotherapeutic approaches, second only to immune checkpoint inhibitors (ICIs), which have already been approved for clinical use. Head and neck squamous cell carcinomas (HNSCCs) are heterogenous epithelial tumors of the upper aerodigestive tract, and a significant proportion of these tumors tend to exhibit unfavorable therapeutic responses to the existing treatment options. Comprehending the immunopathology of these tumors and choosing an appropriate immunotherapeutic maneuver seems to be a promising avenue for solving this problem. The current review provides a detailed overview of the strategies, targets, and candidates for therapeutic vaccination in HNSCC. The classical principle of inducing a potent, antigen-specific, cell-mediated cytotoxicity targeting a specific tumor antigen seems to be the most effective mechanism of therapeutic vaccination, particularly against the human papilloma virus positive subset of HNSCC. However, approaches such as countering the immunosuppressive tumor microenvironment of HNSCC and immune co-stimulatory mechanisms have also been explored recently, with encouraging results.

Head and Neck Squamous Cell Carcinoma Vaccine: Current Landscape and Perspectives

“…Tobacco consumption is the primary risk factor for the development of HPV-negative HNSCC. In addition, betel quid, areca nut, exposure to environmental pollutants, or excessive alcohol consumption is known to synergize with tobacco use to promote carcinogenesis [5,6]. While the tobacco-and alcohol-related neoplasms are decreasing, viral infection is on the rise.…”

“…In addition to the molecular mechanisms of immune escape expressed on the surface of tumor cells, there are several others that involve the tumor microenvironment. These include increases in the percentage of immunosuppressive cells in the tumor matrix (myeloid-derived suppressor cells, tumor-associated macrophages, and T regulatory cells); the secretion of immunosuppressive molecules, such as transforming growth factor-β (TGF-β); and the signal transducer and stimulator of transcription (STAT)-3, as well as the formation of physical barriers and an intricate vascular network that physically prevents the penetration of immune cells into the tumor matrix [5,12].…”

“…The anticancer vaccines under study can be divided into two groups: traditional vaccines that induce a T cell-mediated immune response against specific tumor antigens, and less conventional vaccines targeting immune escape mechanisms [5,11].…”

“…As a result, recombinant vaccines, which are generated through the laboratory synthesis of tumor antigens, are being subjected to more extensive trials. These recombinant vaccines offer potential advantages in terms of standardization and scalability [5].…”

“…However, therapeutic vaccines for HNSCC are still undergoing investigation. Their objective is to induce immunogenicity against HNSCC cells employing a range of mechanisms, including traditional approaches like cell-mediated cytotoxicity induced by antigens, as well as innovative strategies to counteract tumor immune escape mechanisms or stimulate the immune system's cytotoxic activity against neoplastic cells [5]. Here we show an in-depth review of the limitations of current studies and future perspectives in immunotherapy for the treatment of HNSCC to provide a comprehensive overview.…”