Tumor stroma: The Achilles heel of the tumor

Thomas Blankenstein,

Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Straße 10, 13092 Berlin, Germany

It is established that most experimental and probably many human tumors express antigens against which an immune response can be induced. Immunity to transplanted tumors usually relies on T cells, often both CD4⁺ and CD8⁺. Their activation requires antigen cross-presentation by host antigen presenting cell (APC) in draining lymph nodes. Following activation T cells migrate to the tumor site and, when they arrive in time, can reject the tumor. In some tumor models CD4⁺, in other CD8⁺ T cells are the main effectors. Both cell types reject tumors by a similar mechanism. Most importantly, T cells must express IFNg that acts on non-bone marrow derived tumor stroma cells resulting in angiostasis and inhibition of rapid tumor burden. This may allow residual tumor cell elimination by other mechanisms such as direct killing, yet in several models perforin expression by T cells is not necessary. Together, the primary target during tumor rejection is the stroma that is essential for solid tumors and appears to be the most vulnerable component. IFNg producing T cells inhibit the establishment of the stroma, e.g. vascularization, but usually fail against established tumors which could explain why therapeutic vaccination is so notoriously unsuccessful, simply because the T cells come too late.