Mice that lack cbl-b spontaneously reject UV-induced tumors.
Most tumors are poor targets for the immune system as they frequently lack costimulatory molecules and present antigens that are only weakly immunogenic. The few tumor-specific T cells that do get generated are tolerized and fail to see the tumor as a dangerous enemy.
Strategies to induce strong antitumor T cell responses—including cytokine treatment to coax tumors into expressing costimulatory proteins or vaccination with host dendritic cells loaded with tumor antigens—have not always worked. Loeser and colleagues decided instead to circumvent tolerogenic mechanisms within the antitumor T cells themselves.
Their target was the ubiquitin ligase cbl-b, which inhibits TCR signals by targeting downstream signaling proteins for proteasomal degradation. The group had previously shown...
