Innovative appraoches in the treatment of gynaecological and HPV-driven (pre)malignancies

The incidence of endometrial cancer (EC) and tumors caused by human papillomavirus (HPV)—including cervical cancer (CxCa) and head and neck squamous cell carcinoma (HNSCC)—is steadily increasing. Unfortunately, current treatments such as surgery, (chemo)radiotherapy, or combinations thereof often fall short, especially in advanced or recurrent disease.

A key feature shared by these tumors is the presence of tumor-specific antigens: unique proteins capable of activating the immune system. In EC, these are mainly neoantigens, while HPV-related tumors express viral antigens. Tumor-infiltrating lymphocytes, particularly CD8+ T cells, play a key role by penetrating tumors and actively contributing to the recognition and elimination of cancer cells.

This thesis investigates immunomodulatory therapies designed to boost or restore the immune system’s ability to fight cancer more effectively. The approaches studied include immune checkpoint inhibition to block tumor cells’ evasion of immune detection; therapeutic vaccination to enhance the immune response against specific tumor antigens; radiotherapy to improve antigen presentation and make the tumor microenvironment more accessible to immune cells; and genetically engineered T cells that can target cancer cells more precisely.

By strategically combining these innovative therapies with traditional treatments like chemoradiation, the research presented in this thesis aims to pave the way for more effective, durable, and personalized treatments for patients with gynecological and HPV-related cancers.