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Renal cell carcinoma (RCC) infiltrating lymphocytes (TILs) express killer cell immunoglobulinlike receptors (KIRs) that inhibit the antitumor CD8(+) T-cell lysis. In the present study, to better examine the functional consequences of KIR engagement on cytotoxic T lymphocyte (CTL)/tumor interaction, we have investigated the influence of KIR CD158a on early steps of T-cell activation. We show that coengagement of T-cell receptor (TCR) and CD158a by tumor cells inhibited tyrosine phosphorylation of early signaling proteins ZAP-70 and LAT, lipid raft coalescence, and TCR/CD3 accumulation at the CTL/tumor cell interface. In addition, the guanine exchange factor Vav was not phosphorylated, and no actin cytoskeleton rearrangement was observed. Our data indicate a role of KIR CD158a in the dynamic events induced by TCR triggering, preventing CTL membrane reorganization, and subsequent completion of CTL activation program. Accordingly, the expression of CD158 by TILs may favor tumor cell escape to the immune response.

Original publication

DOI

10.1182/blood-2002-02-0643

Type

Journal article

Journal

Blood

Publication Date

15/10/2002

Volume

100

Pages

2874 - 2881

Keywords

Calcium, Carcinoma, Renal Cell, Cell Membrane, Humans, Kidney Neoplasms, Killer Cells, Natural, Membrane Microdomains, Microscopy, Confocal, Phosphorylation, Receptors, Antigen, T-Cell, Receptors, Immunologic, Receptors, KIR, Receptors, KIR2DL1, T-Lymphocytes, Cytotoxic, Tumor Cells, Cultured