Innate and adaptive immune systems are built-in homeostatic functions of many multicellular organisms and protect the host against foreign pathogens and infections. Dysregulation of the molecular mechanisms of the immune system can result in autoimmune diseases. The immune system can also be harnessed and manipulated to provide targeted cancer therapies, some of them relying on the blockade of immune-checkpoint receptors. Two prominent immune checkpoints, PD-1/PD-L1 and CTLA-4/CD80, comprise receptor-ligand pairs that prevent the host immune cells from attacking host tissues. However, cancer cells upregulate the respective PD-L1 and CD80 ligands for PD-1 and CTLA-4 and thereby evade the host-immune response. Therapeutic drugs that block PD-1/PD-L1 and CTLA-4/CD80 interactions re-enable the immune system to attack cancer cells, but their prognostic biomarker remains challenging. In this review, we discuss how the use of quantitative molecular imaging can be exploited to predict the response to anti-PD-1/PD-L1 therapies and to identify cancer patients who would benefit from them.
Keywords: CTLA-4/CD80; FRET/FLIM; PD-1/PD-L1; adaptive immunity; immune checkpoints; immune surveillance; innate immunity.
© 2022 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.