Cancer Immunotherapy: How to Exploit Transposable Elements?

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Abstract
Immunotherapy is one of the most promising advances in the fight against cancer and is beginning to join more conventional treatment approaches such as surgery, radiation therapy, and chemotherapy. A set of strategies consists of ensuring that the immune cells recognize tumor-specific antigens (TSAs) exposed at the surface of tumor cells and eliminate the tumor. TSAs can be processed within tumor cells and presented by human leukocyte antigen (HLA) molecules at the cell membrane, where they can be recognized by cytotoxic T lymphocytes. Additionally, the external region of membrane proteins can act as TSAs independently of HLA presentation. They can be recognized by antibodies, including therapeutic monoclonal antibodies, and thus mark tumor cells for elimination by another set of immune cells. Membrane proteins are also potential targets for chimeric antigen receptor T cells, which are patient-derived T cells engineered ex vivo to recognize a specific antigen in an HLA-independent manner, then expanded and reinjected into the patient. Discovering TSAs with the strongest immunogenicity and specificity is essential for the development of efficient and safe immunotherapies. Moreover, the identification of TSAs that are shared by many tumor types and cases could enable the development of universal and off-the-shelf cancer vaccines or therapies, as opposed to the current state of more personalized but expensive and time-consuming therapies.
Funding Information
  • Agence Nationale de la Recherche
  • Institut National Du Cancer
  • Région Sud
  • Inserm