Immunotherapy in human head and neck cancer

Progress in understanding the immune system and its functions has put emphasis on possible impaired immunological surveillance as one reason for tumorigenesis and progression. As thus, immune surveillance plays a significant role in the control of human cancer.

In the early phase of development of cancer, anti-tumor specific CD8⁺ T cells are able to recognize and eliminate the transformed cells. However, some tumor cells selected under immune pressure survive and evade the immune system. Identification of genes encoding tumor antigens and cytotoxic T lymphocytes specific tumor antigens allowed to postulate that vaccination with appropriately designed immunogens could provide a novel therapy for tumors otherwise resistant to chemo- and radio-therapy regimens.

We are exploring the immunological mechanisms underlying development, progression and recurrence of head and neck cancer in order to develop new concepts for a targeted cancer cell therapy.

The main focus of our research is follow interactions between immune cells and tumor cells and to develop preclinical models for immunotherapy. Our initial results showed that 80% of HNC express at least one tumor associated antigen, which can be recognized by cytotoxic T lymphocytes. In addition, cancer testis antigens, MAGE-A3 and MAGE-A4, are expressed in over 50% of HNSCC. In parallel, we have shown the presence of T lymphocytes able to recognize and generate a specific immune response against these molecules in the peripheral blood of patients with head and neck cancer. These first results confirm our hypothesis that, in this type of cancer, patients develop immune responses against specific tumor antigens.

Furthermore, we have shown that dendritic cells, critical for the efficient activation of cytotoxic T lymphocytes, were weakly present at the tumor microenvironment. Tumor cells expressed molecules such as arginase-2 and cyclooxygenase-2, which block the activity of cytotoxic T lymphocytes. The presence of FOXP3+ T lymphocytes, a subclass of regulatory T cells at the tumor microenvironment, seems to improve significantly the prognosis of patients with HNC. The exact role of such cells remains still unclear but certainly these results confirm the need of immunotherapy-oriented studies for the benefit of a large number of affected patients with the best clinical outcomes. Based on our experience on the analysis of tumour-immune system interactions and on our orthotopic mice model, we plan to investigate whether immunotherapy treatment can enhance tumour regression and control tumour recurrence in HNSCC.

Our research team publications are presented in full in UniSciences, the University of Lausanne Research Database.