HLA class I antigen downregulation in human cancers: T-cell immunotherapy revives an old story.
Human leukocyte antigen (HLA) class I molecule downregulation occurs frequently in many cancers, and this abnormality might adversely affect the clinical course of cancer and the outcome of T-cell-based immunotherapy. Mutations in the HLA class I genes themselves, abnormalities in their regulation and/or defects in HLA class I-dependent antigen processing can underlie HLA class I downregulation. These mutations modulate the susceptibility of tumor cells to in vitro lysis by cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Immune selection of CTL- and NK-cell-resistant tumor cells might explain the rapid progression and poor prognosis of cancers that exhibit HLA class I downregulation. These findings provide compelling evidence that HLA class I downregulation represents a significant challenge for the successful application of T-cell-based immunotherapy of cancer.
Hicklin
D J
DJ
Dept of Immunology, ImClone Systems Incorporated, New York, NY 10014, USA.
Marincola
F M
FM
Ferrone
S
S
D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D007167:Immunotherapy; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology*
D006680:HLA Antigens