title: Host immune response in renal cell cancer: interleukin-4 (IL-4) and IL-10 mRNA are frequently detected in freshly collected tumor-infiltrating lymphocytes.
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 gamma and found to be positive for tumor necrosis factor alpha (TNF alpha), IL-6, IL-1 beta, granulocyte/macrophage-colony-stimulating factor (GM-CSF), and transforming growth factor beta 1 (TGF beta 1) 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, TNF alpha, IL-1 beta, and IL-6 as detected by enzyme-linked immunosorbent assay. Both RCC lines and Wilms tumor lines secreted TGF beta 1. In comparison, normal kidney cells secreted IL-6 and GM-CSF, but not IL-1 beta, or TFG beta 1 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.
authors.affiliation: Department of Surgery, University of Pittsburgh Medical Center, PA 15261, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Maeurer
authors.forename: D M
authors.initials: DM
authors.lastname: Martin
authors.forename: C
authors.initials: C
authors.lastname: Castelli
authors.forename: E
authors.initials: E
authors.lastname: Elder
authors.forename: G
authors.initials: G
authors.lastname: Leder
authors.forename: W J
authors.initials: WJ
authors.lastname: Storkus
authors.forename: M T
authors.initials: MT
authors.lastname: Lotze
mesh_terms: D001483:Base Sequence; D002292:Carcinoma, Renal Cell / Q000276:immunology*; D016207:Cytokines / Q000032:analysis*; D005434:Flow Cytometry; D006801:Humans; D016753:Interleukin-10 / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D007680:Kidney Neoplasms / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000737:chemistry / Q000276:immunology*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis*
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D016753:Interleukin-10; D015847:Interleukin-4