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Immunology

T-Cells Infiltrating Renal Cell Carcinoma Display a Poor Proliferative Response Even Though They Can Produce Interleukin 2 and Express Interleukin 2 Receptors

Jeannine P. Alexander, Seiji Kudoh, Kathryn A. Melsop, Thomas A. Hamilton, Mark G. Edinger, Raymond R. Tubbs, Dante Sica, Laurie Tuason, Eric Klein, Ronald M. Bukowski and James H. Finke
Jeannine P. Alexander
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Seiji Kudoh
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Kathryn A. Melsop
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Thomas A. Hamilton
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Mark G. Edinger
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Raymond R. Tubbs
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Dante Sica
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Laurie Tuason
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Eric Klein
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Ronald M. Bukowski
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James H. Finke
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DOI:  Published March 1993
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Abstract

The fact that progressing tumors contain a significant infiltrate of T-cells brings into question the competency of the infiltrating T-lymphocytes (T-TIL). We have examined the role of the T-cell receptor/CD3 complex and/or the interkeukin 2 receptor (IL2R) in responsiveness of T-cells that infiltrate human renal cell carcinoma. T-TIL display a poor proliferative response to interleukin 2 (IL2) alone, IL2 in combination with antibody to CD3, or mitogen stimulation. The proliferative unresponsiveness was not related to low expression of CD3 or IL2Rβ as the percentage of T-cells expressing CD3 and IL2Rβ were comparable in both T-TIL and peripheral blood T-cells obtained from the same patient. In contrast to the lack of proliferative activity, stimulation of T-TIL or peripheral blood lymphocytes with phytohemagglutinin or anti-CD3 resulted in comparable levels of both IL2 and γ-interferon mRNA and protein expression. While levels of IL2Rα were low in unstimulated T-TIL and peripheral blood lymphocytes, anti-CD3 antibody or IL2 were capable of inducing surface expression of this protein in both cell populations. IL2Rα mRNA levels were comparable in T-cells from the tumor and peripheral blood although in some experiments both the percentage of IL2Rα-positive cells and the density of surface expression per cell were reduced in T-TIL. This reduced IL2Rα expression on T-TIL was not responsible for the proliferative unresponsiveness since T-TIL that expressed both IL2Rα and/or IL2Rβ still failed to respond to high doses of IL2. Thus T-TIL display a selective loss of response to at least two well defined extracellular stimuli. While T-TIL exhibit a poor proliferative response regardless of the form of stimulation these cells remain sensitive to both anti-CD3 and IL2 in terms of IL2 and γ-interferon or IL2Rα expression, respectively. The fact that proliferative unresponsiveness exists even though T-TIL can produce IL2 and express IL2Rα/β suggests that T-TIL have a selective loss of a common intracellular signaling pathway which is requisite to proliferation but not other aspects of response to antigenic stimulation.

Footnotes

  • ↵1 Supported by a contract from the National Cancer Institute (#M47673-03) and USPHS grant CA56937.

  • ↵2 To whom requests for reprints should be addressed, at The Cleveland Clinic Foundation, Department of Urology, 9500 Euclid Avenue, Cleveland, Ohio 44195

  • Received May 12, 1992.
  • Accepted January 11, 1993.
  • ©1993 American Association for Cancer Research.
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March 1993
Volume 53, Issue 6
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T-Cells Infiltrating Renal Cell Carcinoma Display a Poor Proliferative Response Even Though They Can Produce Interleukin 2 and Express Interleukin 2 Receptors
Jeannine P. Alexander, Seiji Kudoh, Kathryn A. Melsop, Thomas A. Hamilton, Mark G. Edinger, Raymond R. Tubbs, Dante Sica, Laurie Tuason, Eric Klein, Ronald M. Bukowski and James H. Finke
Cancer Res March 15 1993 (53) (6) 1380-1387;

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T-Cells Infiltrating Renal Cell Carcinoma Display a Poor Proliferative Response Even Though They Can Produce Interleukin 2 and Express Interleukin 2 Receptors
Jeannine P. Alexander, Seiji Kudoh, Kathryn A. Melsop, Thomas A. Hamilton, Mark G. Edinger, Raymond R. Tubbs, Dante Sica, Laurie Tuason, Eric Klein, Ronald M. Bukowski and James H. Finke
Cancer Res March 15 1993 (53) (6) 1380-1387;
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