Immune Checkpoint Inhibitors: a step forward in cancer management

Cancer cells express unusual antigens which activate signal transduction pathways resulting in unregulated tumor growth. Hence, an effective immune response can be elicited via antibodies targeting the tumoral neoantigens. In particular, modulation of immunological pathways involved in the adaptive immune response is currently considered an innovative approach to fight against aggressive malignancies. Antigen-specific immune responses require critical interaction between antigen presenting cells (APC), T-lymphocytes, and target cells. Upon T-cell activation, the programmed cell death protein-1 (PD-1) blocks the early TCR/CD28 signalling pathway, thus hindering cytokine production and cell cycle progression. Furthermore, cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibits the activated T-cell by binding with high affinity to the B7 molecules and hampering the CD28-mediated signalling. The characterization of these negative immune regulators led to the successful development of fully human monoclonal antibodies (mAbs), specifically designed to promote T-cell activation and increase the anti-tumor immune response. This article provides a brief overview of immune modulation of T-cell function by anti-CTLA-4 and anti-PD-1 antibodies, known as checkpoint inhibitors, and summarizes clinical benefits and limitations of their use in cancer management.