Sci. STKE, 10 February 2004
CANCER BIOLOGY Illuminating Tumors with LIGHT
One reason that tumors continue to grow unabated is that the immune system fails to mount a response to them. Solid tumors consist not only of the cancerous cells, but also a cast of supporting tissue in the form of stroma, which includes fibroblasts and vasculature. The tumor necrosis superfamily member LIGHT binds to the lymphotoxin-β receptor (LTβR) stromal cells and stimulates chemokine and adhesion molecule expression. LIGHT also binds T cells and serves as a costimulatory signal for T cell priming. Yu et al. found that expression of LIGHT, which was engineered to be resistant to proteolysis to increase surface expression, on tumor cells (Ag104 fibrosarcoma expressing the T cell epitope H-2Ld) promoted their rejection upon injection into host mice. The mice exposed to the LIGHT-expressing tumor then also rejected subsequent Ag104Ld tumors, even those not expressing LIGHT. Mice with established Ag104Ld tumors also showed tumor regression if Ag104Ld-LIGHT cells were injected into the tumor or were injected at a distal nontumorous site. Depletion of CD8+ T cells or exposure of the tumor-injected mice to an LTβR-immunoglobulin fusion protein, which competes for stromal LTβR binding of LIGHT, allowed tumor growth to proceed. Analysis of the Ag104Ld-LIGHT tumors from the mice, prior to rejection, showed that the stroma was stimulated to produce several chemokines and the adhesion molecule MAdCAM-1. Furthermore, naïve T cells were recruited to the tumor and activated. Thus, expression of LIGHT on a tumor population may allow the immune system to mount a response promoting the body's natural mechanism for defense against abnormal cells (see Houghton for commentary).
P. Yu, Y. Lee, R. K. Chin, J. Wang, Y. Wang, A. Schietinger, M. Philip, H. Schreiber, Y.-X. Fu, Priming of naïve T cells inside tumors leads to eradication of established tumors. Nat. Immunol. 5, 141-149 (2004). [Online Journal]
A. L. Houghton, LIGHTing the way for tumor immunity. Nat. Immunol. 5, 123-124 (2004). [Online Journal]
Citation: Illuminating Tumors with LIGHT. Sci. STKE 2004, tw46 (2004).
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