Human leukocyte antigen G (
HLA-G) is a nonclassical
MHC class I molecule that exerts important tolerogenic functions. Its main physiologic expression occurs in the placenta, where it participates in the maternal tolerance toward the fetus.
HLA-G expression was found in embryonic tissues, in adult immune privileged organs, and in cells of the hematopoietic lineage. It is expressed in various types of primary solid (
melanoma, head and neck, lung, urogenital, gastrointestinal, and breast
cancers) and
hematologic malignancies (acute
leukemia,
lymphomas) and
metastases.
HLA-G ectopic expression is observed in
cancer, suggesting that its expression is one strategy used by
tumor cells to escape immune surveillance. In this review, we will focus on
HLA-G expression in
cancers and its association with the prognosis. We will highlight the underlying molecular mechanisms of impaired
HLA-G expression, the immune tolerant function of
HLA-G in
tumors, and the potential diagnostic use of membrane-bound and soluble
HLA-G as a
biomarker to identify
tumors and to monitor disease stage. As
HLA-G is a potent immunoinhibitory molecule, its blockade remains an attractive therapeutic strategy against
cancer. Elimination of
HLA-G-expressing
cancer cells would be important in the efficacy of anticancer
therapies.