Immunotherapy and tumour resistance to immune-mediated control and elimination

The field of tumour immunology has gradually reached a consensus that the immune system and tumours sustain a rich set of dynamic interactions starting early during carcinogenesis. Incipient tumours may be eliminated by the immune system via adaptive immune responses mediated mainly by cytotoxic CD8 T lymphocytes, which recognize short antigenic peptides presented by polymorphic major histocompatibility complex (MHC) class I molecules. Advanced tumours, however, are generally highly resistant to the main effectors of the immune system. Moreover, the molecular and cellular composition of the tumour microenvironment is strongly immunosuppressive. Recent research efforts have focused on the dissection of the mechanisms operating at the tumour sites, which neutralize antitumour immunity in both experimental models and directly in cancer patients. All along this basic research, translational scientists have tried to harness the immune system to design novel therapeutic modalities that have collectively been coined as cancer immunotherapy. The overall goal has been to increase the numbers of tumour antigen-specific T cells in cancer patients via either vaccination or adoptive transfer of large numbers of immune cells. It is safe to state that cancer immunotherapy will provide a revolution in the treatment of cancer and the future may bear the prospect of effective tumour control in many cancer types, and that immunotherapy will be one of the main components of effective therapeutic options.