Defective HLA class I antigen processing machinery in cancer

• DOI: 10.1007/s00262-018-2131-2
• Publication Date: 2018-02-27T11:41:56Z
• Authors: Lei Cai; Theodoros Michelakos; Teppei Yamada; Song Fan; Xinhui Wang; Joseph H. Schwab; Cristina R. Ferrone; Soldano Ferrone
• Keywords: Antigen Presentation; 03 medical and health sciences; 0302 clinical medicine; Neoplasms; Histocompatibility Antigens Class I; Humans; 3. Good health

Malignant transformation of cells is frequently associated with defective HLA class I antigen processing machinery (APM) component expression. This abnormality may have functional relevance, since it may have a negative impact on tumor cell recognition by cognate T cells. Furthermore, HLA class I APM abnormalities appear to have clinical significance, since they are associated with poor prognosis in several malignant diseases and may play a role in the resistance to immune checkpoint inhibitor-based immunotherapy. In this paper, we have reviewed the literature describing abnormalities in HLA class I APM component expression in many types of cancer. These abnormalities have been reported in all types of cancer analyzed with a frequency ranging between a minimum of 35.8% in renal cancer and a maximum of 87.9% in thyroid cancer for HLA class I heavy chains. In addition, we have described the molecular mechanisms underlying defects in HLA class I APM component expression and function by malignant cells. Lastly, we have discussed the clinical significance of HLA class I APM component abnormalities in malignant tumors.