HLA class I antigen downregulation in human cancers: T-cell immunotherapy revives an old story

Mol Med Today. 1999 Apr;5(4):178-86. doi: 10.1016/s1357-4310(99)01451-3.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Down-Regulation
  • Gene Expression Regulation, Neoplastic*
  • HLA Antigens / genetics*
  • Humans
  • Immunotherapy
  • Neoplasms / genetics
  • Neoplasms / immunology*
  • Neoplasms / therapy
  • T-Lymphocytes / immunology*


  • HLA Antigens