HLA class I defects in malignant lesions: what have we learned?
Depending on the tumor types, HLA class I antigen downregulation or loss has been found in 16% to 50% of malignant lesions in many malignancies with a clinical association with histopathological markers of poor prognosis of the disease and with reduced free interval and survival. These findings may reflect the escape of tumor cells with HLA class I abnormalities from recognition and destruction by HLA class I-restricted, tumor-associated antigen-specific cytotoxic T lymphocytes. This possibility has stimulated investigations on the mechanisms underlying HLA class I antigen abnormalities in malignant cells. Distinct molecular defects underlying an abnormal HLA class I phenotype have been identified and characterized. These defects range from structural alterations of the genes which encode HLA class I antigen subunits to deregulation of antigen processing machinery components responsible for a functional HLA class I antigen expression. These findings, in conjunction with those of clinical recurrence of lesions with HLA class I antigen loss following T cell-based immunotherapy in patients, suggests that immunoselection may play a role in the generation of malignant lesions with HLA class I antigen abnormalities. This possibility has stressed the need to effectively monitor functional HLA class I antigen expression in malignant lesions in the application of T cell-based immunotherapy as well as to develop strategies to circumvent the negative impact of immunoselection.
Chang
Chien-Chung
CC
Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Campoli
Michael
M
Ferrone
Soldano
S
D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000276:immunology*
D015395:Histocompatibility Antigens Class I