Regulation of the B7-H1 (CD274) inhibitory molecule expression on tumour and immune cells.

The co-stimulatory/inhibitory molecules of family B7 that are expressed on the surface of antigen-presenting and other cells, including tumour cells, play an important role in immune responses regulations. Owing to binding on the T-lymphocyte receptors, they regulate their positive and also negative responses. An important co-stimulatory member of B7 family is B7-H1 molecule. This molecule is presented in many different tissues, not only on haematopoietic cells. However, it is also expressed on tumour cells. Its two binding receptors are in the cytoplasmic membrane of T-cells. The first receptor is unknown and the second receptor is PD-1 (CD279). The linkage between B7-H1 - PD-1 regulates negatively proliferation, differentiation and cytokine secretion of T-cells. This negative regulation is crucial for the constitution of peripheral immune tolerance and also for escape of tumour cells from T-lymphocyte based anti-tumour responses. Although the mechanisms underlying the B7-H1 cell-surface expression have been intensively studied, and they are not fully understood, especially in tumour cells. IFNγ and TNFα regulate B7-H1 expression on transcription level as well as on post- transcription level. Binding sites for transcription factors IRF-1 and NF-κB are located in B7- H1 promoter region. The IRF-1..