The ability of the immune system to identify and destroy nascent tumors, and to thereby function as a primary defense against cancer, has been debated for many decades. Recent findings by a number of investigators in both mouse models of cancer and humans with cancer now offer compelling evidence that particular immune cell types, effector molecules, and pathways can sometimes collectively function as extrinsic tumor suppressor mechanisms. This work provides the basis for further study of natural immunity to cancer and for rational use of this information in the design of immunotherapies in combination with other conventional cancer treatments.
Jeremy B. Swann, Mark J. Smyth
Extrinsic tumor suppression by the immune system.
Transformed cells escaping intrinsic control are subjected to extrinsic tumor suppressor mechanisms that detect and eliminate developing tumors before they become clinically apparent. This is known as the elimination phase of a broader process that has been termed cancer immunoediting. Cancer immunoediting takes into account the observation that the immune system both protects the host against tumor development and promotes tumor growth. Cancer immunoediting is now considered a process composed of 3 phases: elimination, or cancer immune surveillance; equilibrium, a phase of tumor dormancy where tumor cells and immunity enter into a dynamic equilibrium that keeps tumor expansion in check; and escape, where tumor cells emerge that either display reduced immunogenicities or engage a large number of possible immunosuppressive mechanisms to attenuate antitumor immune responses leading to the appearance of progressively growing tumors. These phases have been termed the 3 Es of cancer immunoediting. DR5, death receptor 5; IDO, indoleamine 2,3-dioxygenase; MICA/B, MHC class I chain–related antigens A and B; RAE1, retinoic acid early transcript 1; sMICA/B, soluble MICA/B; ULBP, UL16-binding protein. Figure adapted with permission from