Toward a new stage of PD-1 blockade cancer immunotherapy

Excerpt

In late 1960s, Sir M. Burnet proposed that cancer would be considered within the evolutionary scope of immunological recognition of self and not-self (Cellular Immunology, Melbourne University Press, 1969). In the succeeding decades, many animal studies supporting this proposition have been reported; however, numerous attempts at cancer immunotherapy using various approaches in human cancer patients were unsuccessful. In the midst of frustrating pessimism, G. Klein, a leading cancer immunologist in those days, wrote “Cancer derives from self-somatic cells, and therefore cancer immunity is a matter of breaking self-tolerance, which is a difficult proposition” [1]. T. Honjo’s discovery of PD-1 that is crucial for sustaining self-tolerance [2, 3] led to a breakthrough for cancer immunotherapy: it was demonstrated in animal models that blocking PD-1 function could unleash potential cancer immunity in the host and restrain cancer progression [4]. These findings prompted the application of PD-1 in human cancers, and, a decade later, large-scale clinical trials confirmed that blocking the PD-1/PD-L1 system markedly benefitted patients with several types of advanced cancers [5, 6]. The clinical success of PD-1 blockade immunotherapy convincingly demonstrated for the first time that endogenous immunity in host indeed plays an important part in human cancers. …