Preclinical work has led to an increased understanding of the immunomodulatory 
mechanisms involved in the regulation of the antitumor response in a variety of 
tumor types. PD-1 (programmed death 1) appears to be a key checkpoint involved 
in immune suppression in the tumor microenvironment, even in diseases not 
previously thought to be sensitive to immune manipulation. More recently, the 
subsequent clinical development of PD-1-based therapy has resulted in a major 
breakthrough in the field of oncology. Pembrolizumab, a humanized highly 
selective IgG4 anti-PD-1 monoclonal antibody, was recently approved for the 
treatment of advanced melanoma based on promising early-phase clinical data. 
Encouraging results have also been seen in other malignancies, and PD-1-targeted 
therapies are likely to markedly change the treatment landscape. Future work 
will center on rationally designed combination strategies in order to potentiate 
the antitumor immune response and overcome mechanisms of resistance.