B2M and neoplasm: In a study (12) including four metastatic melanoma patients with AR to pembrolizumab, homozygous B2M frame-shift deletion was detected in a resistant tumor sample, with IHC validating the loss of MHC class I heavy chain at the cancer cell outer-membrane, even though diffuse intracellular staining indicated continued production of MHC class I molecules, in line with the transporting and stabilizing function of beta-2-microglobulin.