Article

Crowe, N. Y., Smyth, M. J. & Godfrey, D. I. A critical role for natural killer T cells in immunosurveillance of methylcholanthrene-induced sarcomas. J. Exp. Med. 196, 119-127

University of Vic, Vic, Catalonia, Spain
Journal of Experimental Medicine (Impact Factor: 12.52). 08/2002; 196(1):119-27. DOI: 10.1084/jem.20020092
Source: PubMed

ABSTRACT

Natural killer (NK) T cells initiate potent antitumor responses when stimulated by exogenous factors such as interleukin (IL)-12 or alpha-galactosylceramide (alpha-GalCer), however, it is not clear whether this reflects a physiological role for these cells in tumor immunity. Through adoptive transfer of NK T cells from wild-type to NK T cell-deficient (T cell receptor [TCR] Jalpha281-/-) mice, we demonstrate a critical role for NK T cells in immunosurveillance of methylcholanthrene (MCA)-induced fibrosarcomas, in the absence of exogenous stimulatory factors. Using the same approach with gene-targeted and/or antibody-depleted donor or recipient mice, we have shown that this effect depends on CD1d recognition and requires the additional involvement of both NK and CD8+ T cells. Interferon-gamma production by both NK T cells and downstream, non-NK T cells, is essential for protection, and perforin production by effector cells, but not NK T cells, is also critical. The protective mechanisms in this more physiologically relevant system are distinct from those associated with alpha-GalCer-induced, NK T cell-mediated, tumor rejection. This study demonstrates that, in addition to their importance in tumor immunotherapy induced by IL-12 or alpha-GalCer, NK T cells can play a critical role in tumor immunosurveillance, at least against MCA-induced sarcomas, in the absence of exogenous stimulation.

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    • "Conversely, administration of í µí»¼-GalCer to mice controlled the growth and metastasis of adoptively transferred [59] [60] or carcinogen-induced [61] [62] or spontaneous [63] tumors. Moreover, adoptive transfer of iNKT cells into Jí µí»¼18−/− iNKT cell-deficient mice prevented the growth of subcutaneous sarcomas [62]. Finally, adoptive transfer of small numbers of purified iNKT cells into lymphocyte-deficient NOD-Scid-IL2rí µí»¾−/− (NSG) mice was sufficient to protect mice from challenge with a CD1d + tumor [64]. "
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    • "Moreover, a number of reports have suggested that iNKT cells play protective as well as tolerogenic roles in tumor immunity [24] [25] [26] [27] [28] [29]. In addition, infiltration of iNKT cells is a prog‐ nostic indicator for colorectal cancer metastasis [29] "

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    • "Moreover, a number of reports have suggested that iNKT cells play protective as well as tolerogenic roles in tumor immunity [24] [25] [26] [27] [28] [29]. In addition, infiltration of iNKT cells is a prog‐ nostic indicator for colorectal cancer metastasis [29] "
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