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Overcoming immune ignorance

CD137 signaling induces a CTL response leading to the regression of established tumors.

Tudor Toma(t.toma@ic.ac.uk)

Enhancing T cell responses with specific mAbs can mediate the regression of selected murine tumors, but several cancers remain resistant to such treatments. In March 1 Journal of Clinical Investigation, Ryan Wilcox and colleagues from Mayo Clinic, Rochester, Minnesota, show that provision of CD137 (a T cell-borne relative of the TNF receptor) signaling associated with an anti-CD13 mAb breaks immunological ignorance and promotes regression of poorly immunogenic tumors.

Wilcox et al. showed that it is immunological ignorance (rather than anergy or deletion of specific cytotoxic T lymphocytes -CTLs) that prevented an anti CD137 mAb from activating tumor immunity in established C3 lymphomas, TC-1 lung carcinoma and B16-F10 melanoma models. But immunization with the CD137 did break the immune ignorance. CD137 immunization was insufficient to stimulate a curative CTL response, but when associated with anti–CD137 mAb induced a CTL response leading to the regression of established tumors (...

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