CTLA4 and metastatic melanoma: Recently, acquired B2M loss also has been identified in a metastatic melanoma patient with secondary resistance to PD-1 blockade [7], in a case of lung cancer that developed resistance to the anti-CTLA-4 + anti-PD-1 combination [8], and in resistant brain metastases in two patients with mismatch-repair deficient colorectal cancer that acquired resistance to anti-PD-1 therapy [13].