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Wednesday, April 27, 2016

Biomarkers Associated with Checkpoint Inhibitors


Checkpoint Inhibitors (CPI), namely anti-CTLA4 and anti-PD1/PD-L1 antibodies, demonstrated efficacy across multiple types of cancer. However, only subgroups of patients respond to these therapies. Additionally, CPI can induce severe immune-related adverse events (irAE). Biomarkers that predict efficacy and toxicity may help define the patients who may benefit the most from these costly and potentially toxic therapies. In this study, we review the main biomarkers that have been associated with the efficacy (pharmacodynamics and clinical benefit) and the toxicity (irAE) of CPIs in patients. 

.....Patients who seem to benefit most from CPIs are those presenting with immunogenic tumors (i.e. with a high mutational load), pre-existing immune response (intratumoral immune infiltrate) and the immune escape ligands being targeted (i.e. PD-L1 for patients treated with anti-PD-1/PD-L1 Abs). Nevertheless, these biomarkers are not perfect. In the future, better knowledge of the mechanisms of action of CPIs in vivo should help us identify other biomarkers in order to define patients who will benefit most from these effective but costly and potentially toxic drug


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