Abstract

Immunotherapy for Head and Neck Cancer

Background: Head and neck cancers (HNC) are malignant tumours that originate from the anatomical structures within the region such as oral cavity, oropharynx, hypopharynx, larynx, sinonasal tract, nasopharynx, salivary glands and thyroid with squamous cell cancer accounting for more than 90% of the histological types. Tobacco and alcohol traditionally have been associated with increased risk of developing HNSCC but more recently studies have implicated human papilloma viruses (HPV) especially type 16 in development of HNSCCs especially those of the oropharynx. Furthermore, patients with immune deficiencies as may be seen in diseases like HIV infection has been shown to be at higher risk of developing HNSCC as compared to others and these have lead to studies on the roles of immune system in development of HNC. There are different traditional treatment modalities for HNC ranging from surgery, chemotherapy, radiotherapy, a combination of any of the modalities sequentially or concurrently. These treatment modalities are associated with significant toxicity and low survivability thus directional change towards newer treatment modalities such as immunotherapy. The concept of immunotherapy in management of cancers was based on the assumption of tumours cells being recognized as foreign rather than as self thus they will be attacked by an activated immune system. The expression of microbial proteins, mutated proteins, and fusion proteins by the tumour cells makes them a target of the body immune defense systems. The body has immune surveillance system in which developing cancer cells are detected and eliminated before they mature. The immune surveillance includes the human leucocyte antigen (HLA) mediate T-lymphocytes and the natural killer cells (NK-cells). These cells with others are responsible for elimination of tumour cells thus halting cancer progression. However, head and neck cancers cells evade the body immune surveillance via their immunogenicity alterations, immune suppressor mediators' production and immune modulators cell types promotion. Squamous cell cancers of head and neck regions usually are immunosuppressive with patients having impaired natural killer (NK) –cell activity and tumorinfiltrating T lymphocytes as well as poor antigen-presenting function as compared to healthy individuals. They are also associated with Tregs cells which secrete suppressive cytokines such as TGF-β and IL-10, express cytotoxic T lymphocyte–associated protein 4 (CTLA-4).