Solid tumors are destroyed (top) only when tumor cells (green) express antigen.

When T cells come across a tumor, they kill off the outer layers and then move in, say Boissonnas et al. on page 345. The authors use intravital microscopy to show that this infiltration and obliteration of the tumor is antigen dependent.

Intravital microscopy has previously revealed the killing strategy of T cells in lymphoid tissue. The T cells use a search-and-destroy tactic, moving rapidly through the tissue while constantly scanning for targets. When an enemy is identified, they stop, kill the intruder, and then resume the hunt. The T cells' method of killing inside a solid nonlymphoid tumor environment, however, is less certain. “We knew that the immune system can reject tumors,” says senior author Sebastian Amigorena, “but we didn't really understand how T cells function inside the tumor.”

Amigorena and his colleagues now show that the initial contact between anti-tumor T cells and their targets is at the tumor periphery. Once the peripheral cells are dead, the T cells attack the next layer and the next, thus gradually diminishing the tumor mass. This method of tumor destruction by T cells is dependent on antigen expression by the tumor cells. In tumors that do not express a cognate antigen, T cells are initially detected in the periphery but then drift away when they fail to find an appropriate target.

The team now plans to use their imaging set-up to investigate whether anti-tumor T cells are doing the killing on their own or, as seen in lymphoid tissue, are recruiting other immune cells. Knowing what cells work against a tumor might lead to anti-tumor strategies that help these cells penetrate to a tumor's depths.