The role of the immune system in the defense against cancer, a process termed tumor immunosurveillance, has been extensively studied. Evidence is accumulating that the molecular organization of proteins and lipids in the plasma membrane of immune cells is of critical importance. Tetraspanin proteins are expressed in the plasma membrane of all mammalian cells and play an important role in the spatial organization of partner molecules into tetraspanin-enriched microdomains. It is now well established that tetraspanins interact with one another as well as with a diverse array of key leukocyte proteins, including immune receptors, integrins, and signaling molecules. These tetraspanin-partner protein interactions control several fundamental cellular processes, which in immune cells involve antigen presentation, motility, proliferation and antibody production. We propose that differences in the tetraspanin microdomain composition account for the abilities of individual tetraspanins to either promote or suppress immune responses. In this review, we discuss novel insights into tetraspanin function in immune cells, and describe how this may control anti-tumor immunity.
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