Abstract
Dysregulated functioning of the immune system is an important part of carcinogenesis and understanding the mechanisms of immune defects can lead to significant improvements of cancer treatments. We have first evaluated molecular defects in lymphoid cells, including NK and T cells, isolated from healthy donors and cancer patients by assessing expression of key molecular regulators, such as c-Myc, Notch1, Notch2, p-53, Cdk6 and Rb. Our results revealed a reduced expression of the proto-oncogene c-myc and Notch1 signaling in the immune cells in patients with cancer. Our latest study was devoted to elucidating whether the decreased expression of c-myc and abnormal Notch1 signaling may be due to a defect in transcription factors associated with their regulation. We assessed the expression of the transcription factor proteins C/EBPα, BACH1 and PU.1 in the immune cells as they play a key role in the differentiation of myeloid and lymphoid cells. We found significant reductions in C/EBPα, BACH1 and PU.1 expression in lymphoid (NK and T cells) as well as myeloid cells in the peripheral blood in patients with cancer. Our data also indicate that molecular defects in the immune system in cancer patients involve cells at different stages of their differentiation, from the early precursors to the mature circulating cells. Further analysis of the expression of other transcription factors in early lymphoid and myeloid progenitor cells should help clarify the regulatory damage of the immune system in oncological processes.