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* Centre d’Immunologie de Marseille-Luminy, Faculté des Sciences de Luminy, Aix-Marseille Université, Marseille, France;
Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 631, Marseille, France;
Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche 6102, Marseille, France;
INSERM/Equipe de Recherche en Méthodologíes 206, Marseille, France; and
¶ CNRS, Groupement de Recherche 2352, Marseille, France
Innate immunity is considered to initiate adaptive antitumor responses. We demonstrate that monoclonal CD8 T lymphocytes reactive to tumor Ag P1A on P815 mastocytoma cells provide essential "help" to NK cells for rejection of P1A-deficient tumors. RAG-deficient mice have normal NK cells but do not reject either tumor. Reconstitution of these mice with P1A-specific T cells conferred resistance to both P1A-expressing and -deficient tumor cells provided they were present at the same site. Elimination of Ag-negative tumor variants required both activated T and NK cells. Gene expression profiling of NK cells infiltrating P1A-positive tumors in mice with specific CD8 T cells demonstrated an activated effector phenotype. However, CD8 T cell help to NK cells appeared ineffective for P1A-negative variants separated from the P1A-positive tumor. Local tumor Ag-specific T cell-NK cell collaboration results in the elimination of tumor cells whether they express or not the T cell tumor Ag epitope, thus containing the emergence of tumor escape variants before metastasis.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by institutional funding from Institut National de la Santé et de la Recherche Médicale and Centre National de la Recherche Scientifique (CNRS), and by grants from Association pour la Recherche sur le Cancer (to A.M.S.V.), Institut National du Cancer (to A.M.S.V. and L.L.), the European Communities (Integrated Project "Cancerimmunotherapy" LSHC-CT-2006-518234 to A.M.S.V.), and the CNRS/Commissariat à l’Energie Atomique Program "Imagerie du Petit Animal" (to L.L. and A.-M.S.-V.). A.S. was supported in part by an International Cancer Research Technology Transfer Fellowship from the International Union Against Cancer. G.V. was the recipient of a Doctoral Fellowship from Ligue Nationale Contre le Cancer.
2 Current address: Laboratory of Experimental Immunology, Cancer and Inflammation Program, Science Applications International Corporation-Frederick, National Cancer Institute, Building 560, Room 31-27, Frederick, MD 21702-1201.
3 A.S. and G.V. are co-first authors.
4 Address correspondence and reprint requests to Dr. Anne-Marie Schmitt-Verhulst, Centre d’Immunologie de Marseille-Luminy, Campus de Luminy, Case 906, 13288 Marseille, Cedex 09, France. E-mail address: verhulst{at}ciml.univ-mrs.fr
5 Abbreviations used in this paper: DC, dendritic cell; 
c, common cytokine receptor -chain; LN, lymph node; DLN, draining LN; TIL, tumor-infiltrating leukocyte; RT, reverse transcription; SSS; second-strand synthesis; EST, expressed sequence tag.
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