Defects in MHC-I antigen presentation represent a common feature of cancer and allow evasion from T cell recognition. Recent findings from immunotherapy in melanoma suggested that irreversible MHC-I defects enable escape from immune pressure. Although loss of antigen presentation is known for many years, strategies to counteract these defects are scarce and largely unexamined. Now that the first forms of T-cell-based immunotherapy show clinical efficacy and reach FDA approval, this issue deserves urgent awareness. Here we describe possible roads leading to corrections of MHC-I defects in tumors and describe a salvage pathway for CTL by targeting novel tumor antigens that we recently uncovered.
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