HLA Antigen Changes in Malignant Tumors of Mammary Epithelial Origin: Molecular Mechanisms and Clinical Implications

As in other types of malignant tumors in humans and in other animal species, malignant transformation of human mammary epithelial cells may be associated with changes in gene expression and in their antigenic profile. Among the latter, loss or downregulation of classical HLA class I antigens (Fig. 1(A)) and induction of non-classical HLA class I antigens (Fig. 1(B)) as well as of HLA class II antigens (Fig. 1(C)) are of particular interest to tumor immunologists and clinical oncologists because of the critical role these antigens play in the generation of tumor antigen (TA)-specific immune responses [1,2], as well as their ability to modulate the interactions of NK cells [3] and T cell subpopulations [4,5] with target cells (Fig. 1(A)). In this chapter we will first discuss the available information about the frequency of abnormalities in classical HLA class I antigen expression in breast carcinoma lesions and the potential underlying molecular defects. Second, we will address the frequency of the non-classical