The link between MHC class I abnormalities of tumors, oncogenes, tumor suppressor genes, and transcription factors

Abstract

MHC class I abnormalities, frequently detected in tumors of distinct origins, are often associated with disease progression and/or poor patient survival. The underlying molecular mechanisms of these defects are either mediated by structural alterations of MHC class I antigens and/or components of the antigen processing machinery (APM) or by their deregulation, which could occur at the transcriptional, post-transcriptional, and/or epigenetic level. Recently, it has been identified that signal transduction pathways, oncogenes, and putative tumor suppressor genes play an important role in controlling the expression of MHC class I APM components in tumor cells. In addition, their expression could be modulated by various factors of the tumor microenvironment, like changes in the pH level, in the metabolism, as well as due to hypoxic conditions. The increased knowledge of MHC class I defects could be employed for (i) the selection of patients undergoing immunotherapies and for (ii) the design of novel therapeutic approaches leading to an induction of MHC class I surface expression, which might enhance the anti-tumor immune response.