Immune Checkpoint Inhibitors for Non-small-cell Lung Cancer: Does that Represent a ‘New Frontier’?
Advances in the interpretation and understanding of cancer behaviour, particularly of its ability to evade the
host immunosurveillance, deregulating the balance between inhibitory and stimulatory factors, led to the development
of an innovative category of immunotherapeutic agents, currently under investigation. Although the disappointing data
deriving from the employment of vaccines in non-small cell lung cancer (NSCLC), more promising results have been
obtained in the early phase trials with immune checkpoint inhibitors, such as cytotoxic T-lymphocyte-associated
antigen-4 (CTLA-4), programmed cell death protein-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors. This
review delineates the main features of the available immunotherapeutic agents, focusing the discussion on immune
checkpoint inhibitors, those that have already demonstrated a relevant clinical activity (such as Ipilimumab and Nivolumab) and those
molecules still in early development phase. Moreover, we underline the possible emerging issues deriving from the progressive diffusion
of Immuno-Oncology into the standard clinical practice. The careful and accurate identification and management of immune-related
toxicities, the validation of more reliable immune response criteria and the increasing research of potential predictive biomarkers are key
points of discussion. The perspective is that immunotherapy might represent an effective ‘magic bullet’, able to change the treatment
paradigm of NSCLC, particularly of those subgroups featured by a heavily mutant cancer (squamous histology and smokers), where the
immunologic agents contribute in cancer development and progression seems to be strong and, concurrently, the efficacy of standard
therapies particularly limited.
Keywords: Checkpoint inhibitors, CTLA-4, immunotherapy, Ipilimumab, Nivolumab, Non-small cell lung cancer, PD-1.
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