Translational Biomedicine

Introduction

Clinicians speculated that patients with proliferative diseases(e.g. leukaemia) might benefit from treatment with agents ofthis type that kill highly proliferating cells. Crucially, introductionof the first chemotherapy agents (analogues of nitrogen mustardgas) meant that cancers which were more complex or hadmetastasised, and could not be successfully treated by surgeryor radiotherapy, could now be addressed. Furthermore,chemotherapy agents have since been developed that work atdifferent stages of the cell cycle, and can be used in combinationto prevent the development of resistance. This concept of usingmodern structural biology and drug discovery methods toproduce small molecules, proteins, antibodies and even cellulartherapies designed to target unique biomarkers associatedwith tumour cells, but not healthy cells, is now considered tobe the ‘gold standard’ approach for discovering new cancertreatments. Immune checkpoint proteins are found on thesurface of T-cells and act as regulators of the immune system.They are crucial for self-tolerance, and prevent the immunesystem from attacking the body’s own cells indiscriminately, thusallowing a distinction to be made between ‘self’ and ‘non-self’.Immune checkpoints also play a vital role in preventinguncontrolled immune responses by modulating the duration andamplitude of a physiological immune response, thus preventingcollateral damage, which is why the term ‘off-switch’ issometimes used to describe their role. It has long been known,but is now increasingly appreciated, that tumour cells can berecognised and disabled by the immune system. Some tumoursshow evidence of spontaneous regression early in theirdevelopment, suggesting that the immune system may becapable of recognising and eliminating early-stage tumour cells.

Conclusion

The immune system has the greatest potential for the specificdestruction of tumours with no toxicity to normal tissue and forlong-term memory that can prevent cancer recurrence. Tumourspecificity of the immune response resides in the recognition oftumour antigens. Viral proteins in tumours caused by virusesand mutated proteins from oncogenes or other genes, as well asnonmutated but abnormally expressed self proteins found on alltumours, have been shown to be good antigens and goodtargets for immunosurveillance. The tumour microenvironmentcan prevent the expansion of tumour antigen-specific helper andcytotoxic T cells and instead promote the production ofproinflammatory cytokines and other factors, leading to theaccumulation of suppressive cell populations that inhibit insteadof promote immunity.