B2M and neoplasm: Significantly, T-cell activity resulting from pMHC-I recognition appears to be the main driver of genetic events resulting in tumor MHC-I downregulation or loss (mutations or LOH in B2M, MHC-I and APM genes) as these were significantly correlated with high T-cell activity [16,60] and were initially subclonal [on repeat biopsies], consistent with the emergence of resistant clones via immune editing within the otherwise immune-competent environment [16,60,66,67].