Is it time to screen for multiple myeloma?

maintained total HLA-I expression despite disruption of multiple HLA-I alleles.This paradox indicates a balance between 2 competing selective pressures: allele-specific HLA-I disruption allows tumor cells to evade neoantigenevoked T-cell recognition, whereas retaining sufficient total HLA-I expression inhibits NK-cell-mediated cytotoxicity.This raises the possibility that therapeutically disrupting this balance could enhance antitumor immunity.Second, the subclonal nature of HLA-I aberrations may suggest that they occur as late events in tumor evolution.However, their high prevalence indicates they are not merely random epiphenomena of genomic instability but represent meaningful adaptive mechanisms.This adaptation is particularly significant given the genomic complexity of advanced CTCL, which increases neoantigen formation.Furthermore, the higher prevalence of mutations in immune surveillance genes (but not other pathways) in samples with HLA abnormalities suggests a coordinated evasion strategy.Likely, tumors with HLA abnormalities continue to face immune pressure from other immune components-evidenced by the dynamic nature of HLA-I abnormalities observeddriving the acquisition of additional mutations to enhance tumor survival.