Appropriate localization and migration of T cells is a prerequisite for antitumor immune surveillance. Studies using fixed tumor samples from human patients have shown that T cells accumulate more efficiently in the stroma than in tumor islets, but the mechanisms by which this occurs are unknown. By combining immunostaining and real-time imaging in viable slices of human lung tumors, we revealed that the density and the orientation of the stromal extracellular matrix likely play key roles in controlling the migration of T cells. Active T cell motility, dependent on chemokines but not on β1 or β2 integrins, was observed in loose fibronectin and collagen regions, whereas T cells migrated poorly in dense matrix areas. Aligned fibers in perivascular regions and around tumor epithelial cell regions dictated the migratory trajectory of T cells and restricted them from entering tumor islets. Consistently, matrix reduction with collagenase increased the ability of T cells to contact cancer cells. Thus, the stromal extracellular matrix influences antitumor immunity by controlling the positioning and migration of T cells. Understanding the mechanisms by which this collagen network is generated has the potential to aid in the development of new therapeutics.

Extracellular adenosine 5'-triphosphate (eATP) is ubiquitously used for cell-to-cell communication. The low concentration of eATP ([eATP]) that exists in a "halo" surrounding resting cells signals the presence of neighboring living cells. Transient increases in [eATP] are used for basic physiological signaling, namely, in the nervous and vascular systems. Larger increases in [eATP] that are associated with cell death serve as a key "danger" signal in inflammatory processes. Two studies now point to roles for ATP in the immune system: providing a costimulatory signal to T cells and driving the differentiation of intestinal T helper 17 (T(H)17) cells.

Immunological synapse formation is usually assumed to require antigen recognition by T cell receptors. However, the immunological synapse formed at the interface between naïve T cells and dendritic cells (DCs) has never been described. We show here that in the absence of antigen, and even of major histocompatibility complex molecules, T cell-DC synapses are formed and lead to several T cell responses: a local increase in tyrosine phosphorylation, small Ca2+ responses, weak proliferation and long-term survival. These responses are triggered more readily in CD4+ T cells than in CD8+ T cells, which express a specific isoform of the repulsive molecule CD43. These phenomena may play a major role in the maintenance of the naïve T cell pool in vivo.