Stimulating CD27 to quantitatively and qualitatively shape adaptive immunity to cancer

The capacity of the immune system to recognize and respond to tumors has been appreciated for over 100 years. However, clinical success has largely depended on the elucidation of the positive and negative regulators of effector cells after their activation via the antigen cell receptor. On the one hand, effector cells upregulate checkpoint molecules that are thought to play a role in limiting immunopathology. On the other, second and third waves of costimulation are often required to promote the expansion, survival and differentiation of effector cells. While it is clear that the immune system can be unleashed by blocking checkpoint molecules, this approach is most effective when pre-existing responses exist in patients' tumors. Thus, coordinating checkpoint blockade with costimulation could potentially expand the patient population that receives benefit from cancer immunotherapy. This review will discuss how the costimulatory molecule CD27 sculpts immunity and preclinical/clinical data indicating its potential for cancer immunotherapy and its clinical translation.