In mice, T cells leave tumors to prevent cancer relapse

Inside melanoma tumors in mice, a red fluorescent tag gave the University of Pittsburgh team a way to follow T cells that had once displayed LAG3, a surface receptor linked to immune exhaustion. The label stayed on permanently, even when the cells stopped producing LAG3.

The experiment revealed a split. Some tagged T cells kept LAG3 and remained inside the tumor. Others lost the marker and moved to the lymph nodes and other tissues. Vaishali Aggarwal, Yangxi (Claudia) Sun, Chang Liu and colleagues called these cells single-positive because they retained the fluorescent label but no longer expressed LAG3.

The team then surgically removed melanoma tumors and waited one month before exposing the mice to the same cancer cells again. The animals were able to clear the secondary tumors, a sign of immune memory. But when the researchers selectively removed the single-positive T cells, tumor growth accelerated sharply. Those departed cells were therefore essential to the long-lasting antitumor response in this experiment.

What does it change, concretely? The finding gives researchers a way to distinguish T cells that remain trapped in a tumor from cells that can leave and seed immune protection elsewhere. Dario A.A. Vignali’s team is now investigating whether blocking LAG3 could increase the mobility of exhausted T cells and strengthen durable immunity. That could eventually inform LAG3-targeting immunotherapies, but these results come from mice; their relevance to patients remains to be tested.