Taking away Cbl-b improves antitumor immune responses

Many researchers are developing ways in which to harness the immune response to treat patients with cancer. However, many results have not been as successful as hoped, largely because tumors develop ways in which to suppress the immune system. For example, before immune cells known as CD8+ T cells can destroy tumors cells they must receive signals through 2 receptors on their cell surface and many tumors do not express the molecules that trigger the second signal, through CD28.

In a study that appears online on March 15 in advance of publication in the April print issue of the Journal of Clinical Investigation, Hua Gu and colleagues show that mouse CD8+ T cells lacking a protein known as Cbl-b can respond in vitro without receiving a signal through CD28. In vivo, when mice lacking Cbl-b were transplanted with tumors they rejected the tumors rapidly, whereas normal mice did not. In addition, if mice that spontaneously develop tumors were engineered to lack Cbl-b the incidence of spontaneous tumor development was markedly decreased. Although these data indicate that ablation of Cbl-b can enhance antitumor immune responses, further studies are needed to determine the short- and long-term impact of Cbl-b ablation before these observations can be translated into the clinic for the treatment of individuals with cancer.-Journal of Clinical Investigation