CTLA4 and melanoma: The effective response rates to anti-CTLA-4 mAb and anti-PD-1 mAb are ~20 and 25%, respectively, in patients with melanoma.453,454 Similarly, additional statistics show that as a single agent, ICIs have response rates in the range 10–35%, which is associated with a limited number of tumor-infiltrating Teff cells, checkpoint disruption, and persistent resistance to checkpoint inhibition.455 Therefore, there is an urgent need to combat therapeutic resistance and identify biomarkers that can be used to predict the response to ICIs.