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

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

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Articles| December 01 1993

Loss of T-Cell Receptor ζ Chain and p56^lck in T-Cells Infiltrating Human Renal Cell Carcinoma^¹

James H. Finke;

James H. Finke

Departments of Immunology, [J. F., J. S., S. K.], Pathology [R. T.], and Urology [E. K.] and Experimental Therapeutic Program [R. B.], Cleveland Clinic Foundation

;

Immunotherapy Laboratory, Program Resources, Inc./DynCorp [A. Z., A. C. O.]

, and

Biological Response Modifiers Program

[D. L. L., H. M., R. W., J. J. O.],

Division of Cancer Treatment, NCI-Frederick Cancer Research and Development Center

,

Frederick, Maryland 21702

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Arnold H. Zea;

Arnold H. Zea

Departments of Immunology, [J. F., J. S., S. K.], Pathology [R. T.], and Urology [E. K.] and Experimental Therapeutic Program [R. B.], Cleveland Clinic Foundation

;

Immunotherapy Laboratory, Program Resources, Inc./DynCorp [A. Z., A. C. O.]

, and

Biological Response Modifiers Program

[D. L. L., H. M., R. W., J. J. O.],

Division of Cancer Treatment, NCI-Frederick Cancer Research and Development Center

,

Frederick, Maryland 21702

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Jill Stanley;

Jill Stanley

Departments of Immunology, [J. F., J. S., S. K.], Pathology [R. T.], and Urology [E. K.] and Experimental Therapeutic Program [R. B.], Cleveland Clinic Foundation

;

Immunotherapy Laboratory, Program Resources, Inc./DynCorp [A. Z., A. C. O.]

, and

Biological Response Modifiers Program

[D. L. L., H. M., R. W., J. J. O.],

Division of Cancer Treatment, NCI-Frederick Cancer Research and Development Center

,

Frederick, Maryland 21702

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Dan L. Longo;

Dan L. Longo

Departments of Immunology, [J. F., J. S., S. K.], Pathology [R. T.], and Urology [E. K.] and Experimental Therapeutic Program [R. B.], Cleveland Clinic Foundation

;

Immunotherapy Laboratory, Program Resources, Inc./DynCorp [A. Z., A. C. O.]

, and

Biological Response Modifiers Program

[D. L. L., H. M., R. W., J. J. O.],

Division of Cancer Treatment, NCI-Frederick Cancer Research and Development Center

,

Frederick, Maryland 21702

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Hiromoto Mizoguchi;

Hiromoto Mizoguchi

Departments of Immunology, [J. F., J. S., S. K.], Pathology [R. T.], and Urology [E. K.] and Experimental Therapeutic Program [R. B.], Cleveland Clinic Foundation

;

Immunotherapy Laboratory, Program Resources, Inc./DynCorp [A. Z., A. C. O.]

, and

Biological Response Modifiers Program

[D. L. L., H. M., R. W., J. J. O.],

Division of Cancer Treatment, NCI-Frederick Cancer Research and Development Center

,

Frederick, Maryland 21702

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Raymond R. Tubbs;

Raymond R. Tubbs

Departments of Immunology, [J. F., J. S., S. K.], Pathology [R. T.], and Urology [E. K.] and Experimental Therapeutic Program [R. B.], Cleveland Clinic Foundation

;

Immunotherapy Laboratory, Program Resources, Inc./DynCorp [A. Z., A. C. O.]

, and

Biological Response Modifiers Program

[D. L. L., H. M., R. W., J. J. O.],

Division of Cancer Treatment, NCI-Frederick Cancer Research and Development Center

,

Frederick, Maryland 21702

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Robert H. Wiltrout;

Robert H. Wiltrout

Departments of Immunology, [J. F., J. S., S. K.], Pathology [R. T.], and Urology [E. K.] and Experimental Therapeutic Program [R. B.], Cleveland Clinic Foundation

;

Immunotherapy Laboratory, Program Resources, Inc./DynCorp [A. Z., A. C. O.]

, and

Biological Response Modifiers Program

[D. L. L., H. M., R. W., J. J. O.],

Division of Cancer Treatment, NCI-Frederick Cancer Research and Development Center

,

Frederick, Maryland 21702

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John J. O'Shea;

John J. O'Shea

Departments of Immunology, [J. F., J. S., S. K.], Pathology [R. T.], and Urology [E. K.] and Experimental Therapeutic Program [R. B.], Cleveland Clinic Foundation

;

Immunotherapy Laboratory, Program Resources, Inc./DynCorp [A. Z., A. C. O.]

, and

Biological Response Modifiers Program

[D. L. L., H. M., R. W., J. J. O.],

Division of Cancer Treatment, NCI-Frederick Cancer Research and Development Center

,

Frederick, Maryland 21702

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Seiji Kudoh;

Seiji Kudoh

Departments of Immunology, [J. F., J. S., S. K.], Pathology [R. T.], and Urology [E. K.] and Experimental Therapeutic Program [R. B.], Cleveland Clinic Foundation

;

Immunotherapy Laboratory, Program Resources, Inc./DynCorp [A. Z., A. C. O.]

, and

Biological Response Modifiers Program

[D. L. L., H. M., R. W., J. J. O.],

Division of Cancer Treatment, NCI-Frederick Cancer Research and Development Center

,

Frederick, Maryland 21702

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Eric Klein;

Eric Klein

Departments of Immunology, [J. F., J. S., S. K.], Pathology [R. T.], and Urology [E. K.] and Experimental Therapeutic Program [R. B.], Cleveland Clinic Foundation

;

Immunotherapy Laboratory, Program Resources, Inc./DynCorp [A. Z., A. C. O.]

, and

Biological Response Modifiers Program

[D. L. L., H. M., R. W., J. J. O.],

Division of Cancer Treatment, NCI-Frederick Cancer Research and Development Center

,

Frederick, Maryland 21702

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Ronald M. Bukowski;

Ronald M. Bukowski

Departments of Immunology, [J. F., J. S., S. K.], Pathology [R. T.], and Urology [E. K.] and Experimental Therapeutic Program [R. B.], Cleveland Clinic Foundation

;

Immunotherapy Laboratory, Program Resources, Inc./DynCorp [A. Z., A. C. O.]

, and

Biological Response Modifiers Program

[D. L. L., H. M., R. W., J. J. O.],

Division of Cancer Treatment, NCI-Frederick Cancer Research and Development Center

,

Frederick, Maryland 21702

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Augusto C. Ochoa

Augusto C. Ochoa ³

Departments of Immunology, [J. F., J. S., S. K.], Pathology [R. T.], and Urology [E. K.] and Experimental Therapeutic Program [R. B.], Cleveland Clinic Foundation

;

Immunotherapy Laboratory, Program Resources, Inc./DynCorp [A. Z., A. C. O.]

, and

Biological Response Modifiers Program

[D. L. L., H. M., R. W., J. J. O.],

Division of Cancer Treatment, NCI-Frederick Cancer Research and Development Center

,

Frederick, Maryland 21702

³To whom requests for reprints should be addressed,at Clinical Services Program, Program Resources, Inc./DynCorp, NCI-FCRDC, P. O. Box B, Frederick, MD 217021201.

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Author & Article Information

²

Both individuals contributed equally to the work presented here.

³To whom requests for reprints should be addressed,at Clinical Services Program, Program Resources, Inc./DynCorp, NCI-FCRDC, P. O. Box B, Frederick, MD 217021201.

Received: August 30 1993

Accepted: October 20 1993

Online ISSN: 1538-7445

Print ISSN: 0008-5472

1993

American Association for Cancer Research, Inc.

Cancer Res (1993) 53 (23): 5613–5616.

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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.

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1993

American Association for Cancer Research, Inc.

Loss of T-Cell Receptor ζ Chain and p56^lck in T-Cells Infiltrating Human Renal Cell Carcinoma^¹

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Loss of T-Cell Receptor ζ Chain and p56^lck in T-Cells Infiltrating Human Renal Cell Carcinoma^¹