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. 1995 Mar;41(2):111–121. doi: 10.1007/BF01527407

Host immune response in renal cell cancer: Interleukin-4 (IL-4) and IL-10 mRNA are frequently detected in freshly collected tumor-infiltrating lymphocytes

Markus J Maeurer 1,✉, Dina M Martin 1, Chiara Castelli 2, Elaine Elder 2, Gerd Leder 3, Walter J Storkus 4, Michael T Lotze 4
PMCID: PMC11037792  PMID: 7656270

Abstract

Human renal cell cancer (RCC) is clearly responsive to immunotherapy. Clinical responses may be mediated by “non-specific” (e. g. natural killer, NK, cells) or “specific” MHC-class-I-restricted tumor-specific CD8+ T lymphocytes. Typically RCC progresses, however, despite significant infiltration of various lymphoid cells. We examined freshly isolated RCC tumor-infiltrating lymphocytes (TIL) derived from seven RCC patients for cytokine expression by the polymerase chain reaction (PCR). Established RCC tumor cell lines derived from these RCC patients were negative for interleukin-2 (IL-2), IL-4, IL-10, and interferon γ and found to be positive for tumor necrosis factor α (TNFα), IL-6, IL-1β, granulocyte/macrophage-colony-stimulating factor (GM-CSF), and transforming growth factor β1 (TGFβ1) message as detected by PCR. An identical pattern of cytokine mRNA expression was identified in other long-term RCC lines and in normal human kidney cells upon culture, but not in two Wilms tumor cell lines tested. Short-term-, and long-term-established RCC lines, but not Wilms tumor lines, secreted substantial levels of GM-CSF, TNFα, IL-1β, and IL-6 as detected by enzyme-linked immunosorbent assay. Both RCC lines and Wilms tumor lines secreted TGFβ1. In comparison, normal kidney cells secreted IL-6 and GM-CSF, but not IL-1β, or TFGβ1 under identical in vitro cell culture conditions. We applied PCR-based methods to characterize the cytokine mRNA expression pattern in immune cells infiltrating into renal cell cancer without the need for expansion of such effector cells in vitro. Examining freshly collected RCC TIL by PCR from patients with primary cell cell cancer, we could demonstrate that such cells, but not lympho-mononuclear cells harvested from normal human kidney tissue, typically exhibit IL-4 and IL-10 mRNA expression.

Key words: Renal cell cancer, Tumor-infiltrating lymphocytes (TIL), Interleukin-10

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