First, disruption of MHC class I and/or II (concurrent disruption in four PD1 PROGs) was found in 6/22 (27%) PD1 PROG melanomas and was driven by independent mechanisms, including genetic alterations affecting B2M, epigenetic dysregulation of the MHC-II transcription regulator CIITA, and loss of heterozygosity across the chromosome 6p MHC-I/II locus. Here, B2M is linked to melanoma.