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The in vitro effects of interleukin-12 upon tumor-infiltrating lymphocytes derived from renal cell carcinoma

  • Original Paper
  • Experimental Oncology
  • Published:
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Abstract

Clinical trials utilising interleukin (IL)-2 with tumor-infiltrating lymphocytes (TIL) have demonstrated efficacy in the treatment of metastatic renal cell carcinoma (RCC). Several cytokines, as well as growth factors have demonstrated modulatory effects upon the biological properties of TIL from RCC, suggesting a potentially important role for cytokines other than IL-2 in the development of active and tumor-specific TIL. IL-12 was recently characterized as a natural-killer-cellstimulatory factor or cytotoxic-T-cell-maturation factor. These properties of IL-12 prompted us to investigate the impact of this cytokine upon the activation of TIL from human RCC. In an attempt to enhance the in vitro growth and activity of renal TIL, we have grown eight renal TIL cultures in varying concentrations of IL-2 (8, 40, 80, 400 U/ml) and IL-12 (200 U/ml). In addition, IL-12 (200 U/ml) was added to TIL cultures pre-activated with IL-2 (400 U/ml). Growth, cell expansion, and the ability of TIL to release certain cytokines upon tumor stimulation were determined. Proliferation assays, phenotypic analysis, and cytotoxicity assays were performed at an early and a late culture stage. IL-12, alone and when added to suboptimal concentrations of IL-2, failed to induce TIL growth. While the addition of IL-12 to optimal doses of IL-2 suppressed TIL culture expansion, sequential culture exposure first to IL-2 and then to IL-2+IL-12 increased the number of cells expressing CD3+/CD56+ and these cultures demonstrated enhanced in vitro lysis of autologous tumor. IL-12 clearly demonstrated a sequence-dependent impact of the biological behaviour of TIL from RCC. The optimal use of IL-12 in the in vitro expansion of renal TIL may result in cells with an enhanced specific anti-tumor effect.

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Abbreviations

IL :

interleukin

TIL :

tumor-infiltrating lymphocytes

RCC :

renal cell carcinoma

NK :

natural killer

IFN :

interferon

TNF :

tumor necrosis factor

GM-CSF :

granulocyte/macrophage-colony-stimulating factor

LAK :

lymphokine-activated killer cells

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Authors and Affiliations

  1. Department of Internal Medicine I, Division of Oncology, University of Vienna, Währinger Gürtel 18-20, A-1090, Vienna, Austria

    Günther G. Steger (G.G. Steger is a recipient of a 1990 Max Kade Research grant), Manuela P. Djavanmard & Robert M. Mader

  2. Department of Surgery, University of Vienna, Wahringer Gürtel 18-20, A-1090, Vienna, Austria

    Michael F. Gnant & Raimund Jakesz

  3. Department of Surgery, Division of Urology, UCLA-School of Medicine Los Angeles, 10833 Le Conte Avenue, 90024-1738, Los Angeles, CA, USA

    Jean B. deKernion & Arie Belldegrun

  4. the Jonsson Comprehensive Cancer Center, 10833 Le Conte Avenue, 90024-1738, Los Angeles, CA, USA

    William Pierce, Jean B. deKernion, Robert Figlin & Arie Belldegrun

  5. Department of Medicine, Division of Hematology-Oncology, UCLA-School of Medicine Los Angeles, 10833 Le Conte Avenue, 90024-1738, Los Angeles, CA, USA

    William Pierce & Robert Figlin

Authors
  1. Günther G. Steger
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  2. Michael F. Gnant
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  3. Manuela P. Djavanmard
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  4. Robert M. Mader
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  5. Raimund Jakesz
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  6. William Pierce
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  7. Jean B. deKernion
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  8. Robert Figlin
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  9. Arie Belldegrun
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Correspondence to Günther G. Steger.

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Steger, G.G., Gnant, M.F., Djavanmard, M.P. et al. The in vitro effects of interleukin-12 upon tumor-infiltrating lymphocytes derived from renal cell carcinoma. J Cancer Res Clin Oncol 123, 317–324 (1997). https://doi.org/10.1007/BF01438307

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  • DOI: https://doi.org/10.1007/BF01438307

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