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Tumor Cells Regulate the Lytic Activity of Tumor-specific Cytotoxic T Lymphocytes by Modulating the Inhibitory Natural Killer Receptor Function¹

INSERM U487, Institut Fédératif de Recherche (IFR 54) [A. G., N. G., S. C., A. C.], Unité d’Immunologie Clinique [E. A.], Institut Gustave Roussy, 94805 Villejuif, France; INSERM U508, Hôpital Paul Brousse, 94805 Villejuif, France [J. G-M., B. A.]; and Dipartimento di Medicina Sperimentale, Universita di Genova, 16132 Genova, Italy [A. M.]

Tumor-infiltrating p58⁺ T cells from a renal tumor were specifically expanded in response to tumor cell stimulation and cloned. These p58⁺ T cells were found to express a memory phenotype and corresponded to clonal TCRBV3 T-cell expansion. Functionally, p58⁺ CTLs displayed a low lytic activity for HLA-A2 tumor and normal cells. However, this lytic activity was significantly increased after blockade of p58 with specific monoclonal antibodies. Interestingly, we demonstrated that stimulation by tumor cells was required to trigger the inhibitory effect of p58 on the lytic activity of antigen-specific CTLs and that stimulation of the inhibitory function of p58 by tumor cells correlated with an inhibition of nuclear factor-B activation in p58⁺ tumor-specific CTLs.

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