Immune response to brain tumors

Abstract The significance of the immune system in the recognition and rejection of tumor cells in general is highly debated. Nevertheless, glioblastoma may escape immune surveillance by producing transforming growth factor β2 (TGF-β2), which inhibits growth and function of the cellular elements of the immune system. Escape from TGF-β dependent immune suppression may be achieved by the loss of TGF-β receptors on lymphocytes or by the production of protease inhibitors; in glioblastoma cells the latter block the protease-dependent events of processing of latent TGF-β2 into the mature, bioactive form. In the absence of the production of bioactive TGF-β by glioblastoma cells, the immune amplification system of the central nervous system, which comprises astrocytes and microglia cells, is suggested to enable immune effector pathways to recognize and reject tumor cells. Tumor immune surveillance could even be facilitated by glioblastoma cells, which secrete cytokines including chemotactic factors and express major histocompatibility complex (MHC) class I and II antigens. This, however, would not only exclude secretion of TGF-β but would also require both the expression of tumor neoantigens and an absence of immune tolerance to these antigens. Both features have not yet been clarified.