Loss of HLA-class-I expression in non-small-cell lung cancer: Association with prognosis and anaerobic metabolism

Cancer immuno-editing frequently leads to loss of HLA-class-I molecule (HLA) expression and impaired immune surveillance. We investigated the expression of HLAs in a series of operable non-small-cell lung carcinomas (NSCLCs). Complete loss and extensive loss of expression was noted in 41.5% and 23.4% of cases, respectively. Low CD8 + and FOXP3 + TIL-density was significantly associated with loss of HLAs (p < 0.05 and p = 0.003, respectively). High PD-L1 expression was linked with sustained expression of HLAs. A significant association of loss of HLA-expression with overexpression of LDH5 (p = 0.01) and marginally with HIF1α was recorded. Cell line experiments confirmed that hypoxia and acidity down-regulate the expression of HLAs. A direct association between HLAs and Beclin-1 expression was also noted (p = 0.01). Loss of HLA-expression was linked with poorer survival (p < 0.01), independent of stage. It is concluded that loss of HLA-class-I molecules is frequent in NSCLC and directly linked to micro-environmental hypoxia and acidity.