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 Blood, 15 March 2005, Vol. 105, No. 6, pp. 2428-2435.
Prepublished online as a Blood First Edition Paper on November 9, 2004; DOI 10.1182/blood-2004-09-3458.

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IMMUNOBIOLOGY

NK cells that are activated by CXCL10 can kill dormant tumor cells that resist CTL-mediated lysis and can express B7-H1 that stimulates T cells

Aurore Saudemont, Nathalie Jouy, Dominique Hetuin, and Bruno Quesnel

From the Institut National de la Santé et de Recherche Médicale (INSERM) Unité 524, Institut de Recherche sur le Cancer de Lille, Lille, France; Institut Fédératif de Recherche 114, Lille, France; and Service des Maladies du Sang, Centre Hospitalier et Universitaire de Lille, Lille, France.

Tumor dormancy is a phenomenon where small numbers of tumor cells persist in the host for months or years. We previously showed in the DA1-3b/C3H mouse model of acute myeloid leukemia that dormant tumor cells resist cytotoxic T-lymphocyte (CTL)–mediated killing because they overexpress B7-H1. Here, we vaccinated mice with DA1-3b cells transduced with CXCL10. Vaccinated mice developed a strong systemic immunity that led to the cure of established leukemia without persistence of dormant tumor cells. In vivo depletion of natural killer (NK) cells from the mice abrogated the protective effect of the vaccine. Long-term persistent leukemic cells resist CTL-mediated lysis but were killed by NK cells from mice vaccinated with DA1-3b/CXCL10. These NK cells expressed B7-H1. Recombinant CXCL10, CXCL9, CXCL11, and CXCL12 chemokines induced expression of B7-H1 on mouse and human NK cells in vitro. Mouse and human B7-H1+ NK cells induced proliferation of T cells and production of interferon {gamma} and tumor necrosis factor {alpha} in vitro, and in vivo blocking of B7-H1 inhibited the protective effect of vaccination. Thus, CXCL10 induces antileukemic immunity, at least partially by stimulating NK cells to express B7-H1+. This antitumor effect is in contrast to the effect of B7-H1 when expressed on tumor cells because it stops cytotoxic lymphocytes from killing those tumor cells.


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B7-H1 connection of innate and adaptive immunity against tumor dormancy
Lieping Chen
Blood 2005 105: 2242-2243. [Full Text] [PDF]



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