page 907, because endogenous cells steal necessary activating cytokines. This limits the ability of the transferred cells to launch an antitumor attack in mice.
Elimination of the body's lymphocytes followed by infusion of tumor-specific CD8+ T cells has recently been shown to help destroy established tumors in humans. Studies in mice have suggested that irradiation works in two ways. The depletion of host cells creates empty space, which the transferred cells can fill by homeostatic proliferation. The depletion also rids the host of regulatory T (T reg) cells, which would otherwise dampen the function of the transferred antitumor cells.
Gattinoni and colleagues now add a new wrinkle to this story. They confirmed that tumor-specific T cells combated aggressive skin tumors more effectively in irradiated mice than in nonirradiated controls. To the authors' surprise, the antitumor T cells increased to equivalent numbers in both mice. The cells transferred into the depleted mice, however, became more activated and secreted more cytokines.
The increased activation was not due to depletion of T reg cells, as irradiation boosted antitumor responses in mice lacking these cells. Rather, the immune depletion freed up activating cytokines, such as interleukin-7 and -15, which were being consumed by endogenous cells. Thus, supplementing tumor-specific T cell transfers with activating cytokines might improve upon this revolutionary antitumor therapy.