Anti-cancer vaccines: What future in anti-cancer immunotherapy strategies?

Abstract

Tumor cells can be recognized by the immune system and in particular by cytotoxic CD8+T cells. From this observation was derived the concept that vaccination targeting these tumor-associated molecules was feasible. Preventive cancer vaccines targeting oncogenic papillomavirus or hepatitis B virus do exist and are efficient. They aim at preventing the introduction into the body of viruses that play a role in oncogenesis. To date, in the case of an already grown cancer, the anti-tumor vaccines have had no impact on the care of patients. These vaccines are gaining renewed interest, as new antigenic targets have emerged and have been incorporated into the design of vaccines, such as mutated antigens which appeared to be more immunogenic. Less editing cells than tumor cells in the tumor microenvironment, such as protumor endothelial cells or fibroblasts, could also be eliminated by cancer vaccines. New vaccine efficacy criteria have been identified, such as the need to induce intratumoral resident T lymphocytes thanks to the development of mucosal vaccination to amplify them. Finally, because of the immunosuppression of the tumor microenvironment and the expression of inhibitory receptors on CD8+T cells in the tumor, various therapeutic association strategies between the anti-cancer vaccines and molecules supporting these inhibitions are currently used in clinical development. Especially, the efficacy of antibodies against costimulatory inhibitory molecules (PD-1, PD-L1…) relies on the presence of pre-existing CD8+T cells occurring in 25-30% of cancer patients. For the 70% resistant patients, cancer vaccine may reprogram this tumor environment via the induction of intratumoral CD8+T cells which will very likely counteract this resistance to anti-PD-1/PD-L1 antibodies.