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. 2021 Aug 5;9(8):e002899. doi: 10.1136/jitc-2021-002899

Figure 3.

Figure 3

Type of classical HLA-I alterations in cancer cells. Various HLA-I abnormal cancer phenotypes can form depending on whether these abnormalities are caused by genetic or non-genetic defects. The striking difference between these defects is genetic aberration-originated HLA-I dysregulation cannot be recovered by pharmaceutical or IFN treatment. The most frequently formed genetic abnormality is LOH at chromosome 6 which leads to loss of maternal or paternal HLA haplotypes. Heavy chain mutations or β2M mutations causes complete loss of HLA function. HLA allelic loss may occur in the case of locus-specific mutations. Any mutations in IFN signaling pathway or APM genes may lead to complete loss or down regulation of HLA-I expression. On the other hand, cancer-specific transcriptional down regulation of HLA-I genes or APM genes, epigenetic changes such as methylation or acetylation, autophagy-mediated degradation, stress and hypoxia can lead to HLA-I expression dysregulation. However, HLA-I can be recovered by using different treatment approaches in accordance with the specific type of defect. APM, antigen presentation machinery; β2M, β−2-microglobulin; IFN, interferon; LOH, loss of heterozygosity; HLA, human leucocyte antigen.