Immunogenic cell death and immunogenic surrender: related but distinct mechanisms of immune surveillance
Rosanna Mezzapelle, Marco E. Bianchi, Massimo P. Crippa
Abstract
The success of immunotherapies has demonstrated to what extent the immune system can detect, keep in check, and sometimes reverse the development of cancer [ 1 ]. Current immunotherapies focus on disabling the PD-1 or CTLA-4 systems, which restrain the activity of cytotoxic T lymphocytes that recognize tumor neoantigens. However, the selection and expansion of such cytotoxic T lymphocyte clones depend on tumor antigen cross-presentation and T cell priming in the first place. If antigens are not detected by the immune system, no immune responses can take place. Dendritic cells sample the microenvironment by phagocytosing exosomes released by living cells or apoptotic bodies deriving from apoptotic cells, and will cross-present new epitopes these contain. Arguably, cells or exosomes bearing neoantigens are not sufficient to elicit a durable immune response; in fact, the same mutational mechanisms generate neoantigens in cancer cells and in aging cells, and yet most aged somatic cells escape the recognition and elimination by the immune system.