Loss of T-Cell Receptor ζ Chain and p56lck in T-Cells Infiltrating Human Renal Cell Carcinoma

James H. Finke; Arnold H. Zea; Jill Stanley; Dan L. Longo; Hiromoto Mizoguchi; Raymond R. Tubbs; Robert H. Wiltrout; John J. O'Shea; Seiji Kudoh; Eric Klein; Ronald M. Bukowski; Augusto C. Ochoa

DOI: Published December 1993

Abstract

Cancer patients and mice bearing tumors develop a progressive immunosuppression manifested by a decreased delayed-type hypersensitivity, decreased T-cell lytic activity, diminished production of lymphokines, and a reduced T-cell proliferative response. The mechanisms underlying these changes are incompletely understood. We recently reported the presence of marked alterations in signal transduction in T-cells from mice bearing long-term (28-day) tumors. We hypothesized that a soluble product produced by the tumor or resulting from the immune response to tumor might be responsible for inducing the changes in T-cells. Tumor-infiltrating lymphocytes from patients with renal cell carcinoma tested here showed, in 10 of 11 cases, a marked decrease in the expression of the T-cell receptor ζ chain and in p56^lck tyrosine kinase. The presence of major alterations in the tumor-infiltrating lymphocytes with only minor changes in the peripheral blood leukocyte T-cells supports the notion that the defects are induced by exposure to tumor. These results suggest that tumor-infiltrating lymphocytes may be compromised in their antitumor efficacy in patients with renal cell cancer.

Footnotes

↵¹ Supported in part by USPHS Grants CA56937 and CA 48919 (J. F.); also supported, at least in part, by the National Cancer Institute, Department of Health and Human Services under Contract N01-C0-74102 with Program Resources, Incorporated/DynCorp, and CRADA CACR 0109 with OncoTherapeutics, Inc. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the United States Government. By acceptance of this article, the publisher or recipient acknowledges the right of the U.S. Government to retain a nonexclusive, royalty-tree license in and to any copyright covering the article.
↵² Both individuals contributed equally to the work presented here.
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