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Intratumor CD4 T-Cell Accumulation Requires Stronger Priming than for Expansion and Lymphokine Secretion

Laboratoire d'Immunologie pré-clinique, Institut National de la Sante et de la Recherche Medicale U653, Institut Curie, Paris, France

Requests for reprints: Olivier Lantz, Laboratoire d'Immunologie pré-clinique, Institut National de la Sante et de la Recherche Medicale U653, Institut Curie, 26 rue d'Ulm, 75005 Paris, France. Phone: 33-144-324-218; Fax: 33-144-324-444; E-mail: Olivier.lantz{at}curie.net.

T cells need to migrate to and accumulate inside tumors before mediating rejection of the tumor. The number of specific T cells inside tumors may depend on the efficiency of priming in the draining lymph node (DLN), intratumor deletion, suppressive phenomena, or both. We used monoclonal anti-male antigen CD4 (Marilyn) T cells and tumor cell lines expressing or not the corresponding antigen (Dby) to analyze CD4 T-cell accumulation in tumors. Priming by MHC II⁺ or MHC II^– male splenocytes or Dby⁺ tumor cells induced similar Marilyn T-cell expansion in the DLN and recirculation in other lymph nodes and capacity to produce IFN-. However, intratumor accumulation was different for each priming condition. In mice with Dby^– tumors, MHC II⁺ male splenocyte priming induced greater, although not statistically significant, Marilyn T-cell accumulation in the tumors than MHC II^– male splenocyte priming. In mice with Dby⁺ tumors, priming in the tumor DLN induced less Marilyn T-cell intratumor accumulation than priming by MHC II⁺ male splenocytes. We saw comparable differences for Marilyn T-cell accumulation in gut lamina propria, suggesting that priming affects effector T-cell accumulation in inflamed tissues. Mature dendritic cells were loaded with graded doses of Dby peptide to control for antigen-presenting cell characteristics during priming. We observed similar proliferation, with higher concentrations inducing higher intratumor accumulation. Thus, intratumor accumulation requires stronger stimulation than for proliferation or the capacity to secrete lymphokines. In this system, priming intensity alone can explain the number of intratumor T cells without having to call for intratumor deletion or suppression phenomena. (Cancer Res 2006; 66(10): 5443-51)

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