Modulation of membrane proteins by vertical phase separation and membrane lipid fluidity. Basis for a new approach to tumor immunotherapy.

Cell differentiation and proliferation entail a series of membranal events, which lead to the modulation of proteins at the cell surface. In the case of malignant differentiation this offers the tumor cell the possibility of escaping immune surveillance. Vertical phase separation of membrane proteins appears to play an important role during modulation of membrane proteins. The data reviewed here strongly suggests that the membrane lipid fluidity modulates expression of membrane proteins by vertical phase separation. When the membrane fluidity was elevated the surface expression of some membrane proteins increased, whereas it decreased when the membrane became more rigid. These proteins (e.g. H-2 antigens, hormone receptors and others were termed "syndromic". The membrane proteins which displayed the opposite behaviour with respect to the lipid fluidity were referred to as "antidromic" proteins e.g. human blood group antigens, Thy 1.2 and neuroreceptors). The possibility that the tumor cell plasma membrane contains cryptic antidromic antigens which may become exposed when the membrane lipid fluidity is manipulated has triggered a potentially new experimental approach in the treatment of neoplastic diseases. Autologous tumor cells pretreated to decrease their membrane lipid fluidity were shown to have an increased capability of eliciting specific immune responses when compared to normal control cells subjected to the same treatment.