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Impaired Signal Transduction in Tumor Infiltrating T Cells from Patients with Renal Cell Carcinoma

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Biology of Renal Cell Carcinoma

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Abstract

T cell activation in response to antigen requires interaction of multiple receptor-coreceptor pairs (1–3). Important outcomes of T cell stimulation include cellular proliferation, cytokine secretion and cytotoxic activity (1). The induction of these various functions is dependent on the activation of intracellular signal transduction pathways which are linked to the different receptors (4). Activation of the T-cell receptor complex (TCR-CD3) involves antigen recognition through the α /β subunits and intracellular signaling via CD3 (γ,δ,ε) and ζ chains (1,2,5). Tyrosine phosphorylation of several proteins such as TCR ζ, CD3 ε, and phospholipase C- γ represent an important early event (1,2, 4–6). Three different proteins kinases (PTK) have been implicated in TCR/CD3 signaling and they include p56lck, p59fyn and ZAP-70 (2,4,5,7–9). Tyrosine phosphorylation leads to several intermediate signaling events that include the formation of second messengers and the activation of serine/threonine kinases along with phosphatases which are important for downstream gene expression (4). IL2 binding to its receptor is an important step in T cell activation and proliferation (10). This receptor is a trimolecular complex in which the IL2Rα chain is necessary for high affinity receptor expression while the β and γ chains are involved in signal transduction (11–14). Although the IL2R signaling pathway is not well defined, tyrosine phosphorylation of several substrates appears to be an essential early event (12,14–16).

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Authors and Affiliations

  1. Department of Immunology, The Cleveland Clinic Foundation, Cleveland, Ohio, USA

    James Finke Ph.D., Seiji Kudoh M.D., D.Sc., Jill Stanley B.S., Xiaoli Li Ph.D., Qiu Wang Ph.D., M.D., Jeong-Kyu Park Ph.D., Jun Liu M.D., Vladimir Kolenko Ph.D., M.D. & Patricia Rayman M.S.

  2. Department of Urology, The Cleveland Clinic Foundation, Cleveland, Ohio, USA

    Eric Klein M.D.

  3. Department of Clinical Pathology, The Cleveland Clinic Foundation, Cleveland, Ohio, USA

    Raymond Tubbs D.O.

  4. Department of Hematology and Medical Oncology, The Cleveland Clinic Foundation, Cleveland, Ohio, USA

    Ronald M. Bukowski M.D.

  5. Cancer Center Experimental Therapeutics Program, The Cleveland Clinic Foundation, Cleveland, Ohio, USA

    Ronald M. Bukowski M.D.

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  1. James Finke Ph.D.
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  2. Seiji Kudoh M.D., D.Sc.
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Finke, J. et al. (1995). Impaired Signal Transduction in Tumor Infiltrating T Cells from Patients with Renal Cell Carcinoma. In: Biology of Renal Cell Carcinoma. Springer, New York, NY. https://doi.org/10.1007/978-1-4612-2536-2_8

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  • DOI: https://doi.org/10.1007/978-1-4612-2536-2_8

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4612-7571-8

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