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

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.