Tumor-Tunneling T Cells

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Science  09 Mar 2007:
Vol. 315, Issue 5817, pp. 1339
DOI: 10.1126/science.315.5817.1339c

T cell responses begin inside the lymph nodes and spleen, and considerable headway has been made in monitoring how these immune cells behave at these sites through live intravital imaging techniques. A natural extension of this is to visualize how activated T cells conduct themselves once they've migrated to inflamed tissues, or tumors.

Boissonnas et al. have combined immunofluorescence with intravital microscopy to follow cytotoxic T lymphocytes (CTLs) as they destroy tumors in vivo. Tumor cells were inoculated into mice at two separate sites, but with those at only one site engineered to express antigen to which T cells could respond. Although the solid tumors that formed at both sites became infiltrated with T cells, this predominated in the antigen-expressing tumors. The behavior of the infiltrating T cells was also measurably different, with those in the antigen-bearing tumor displaying strong signs of activation and distinct migration patterns. In particular, the tumor-reactive CTLs initially displayed diminished motility, which they regained as tumor cells were killed off. These CTLs also burrowed more vigorously into the tumors that expressed antigen. It will now be interesting to determine if similar behavior occurs in other tumor settings (for example, where less potent antigens are expressed) or in nonmalignant tissues where CTLs also mediate cellular destruction (for example, in autoimmune diseases). — SJS

J. Exp. Med. 204, 345 (2007).

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