Lack of interleukin‐2 (IL‐2) expression and selective expression of IL‐10 mRNA in human renal cell carcinoma

Freshly isolated tumor‐infiltrating lymphocytes (TIL) are often functionally deficient. Since one of the key functional parameters of an immune response is the local production of cytokines, we studied the expression of cytokine genes in freshly isolated renal cancer tissue. Using a PCR‐assisted mRNA amplification assay, the constitutive expression of mRNA for 10 different cytokines was assessed in renal cancer tissue. We compared the cytokine mRNA expression in freshly isolated samples of renal carcinomas, renal cancer cell lines established from the tumor samples, peripheral blood mononuclear cells (PBMC) and non‐tumor kidney tissue isolated from the same patients. IL‐10 mRNA expression was detected only in tumor samples, while renal cancer lines, PBMC and non‐tumorous kidney tissues were devoid of this cytokine. One‐third of the tumor samples but none of the normal kidney samples also expressed G‐CSF mRNA. IL‐6, TNF‐α and IFN‐γ mRNA were expressed non‐selectively in tumors, PBMC and normal renal tissue. Expression of IL‐2, IL‐3 and IL‐4 mRNA was not detected in any of the tissues analyzed. Established renal cancer lines exhibited expression of IL‐lα, IL‐6, TNF‐α and GM‐CSF. Culture of tumor‐derived T cells with anti‐CD3 monoclonal antibody (MAb) resulted in expression of IL‐2, IL‐3 and IL‐4 mRNA. In contrast, none of these cytokines was detected in culture with recombinant human IL‐2 alone. Since IL‐10 is known to suppress antigen presentation, these findings have important implications for the possible in vivo role of IL‐10 as a suppressor of local anti‐tumor response.

[1]  M. Matsuda,et al.  IL-10 converts mouse lymphoma cells to a CTL-resistant, NK-sensitive phenotype with low but peptide-inducible MHC class I expression. , 1995, Journal of immunology.

[2]  M. Matsuda,et al.  Interleukin 10 pretreatment protects target cells from tumor- and allo- specific cytotoxic T cells and downregulates HLA class I expression , 1994, The Journal of experimental medicine.

[3]  D. Longo,et al.  Loss of T-cell receptor zeta chain and p56lck in T-cells infiltrating human renal cell carcinoma. , 1993, Cancer research.

[4]  M. Matsuda,et al.  Decreased expression of the signal-transducing zeta chains in tumor-infiltrating T-cells and NK cells of patients with colorectal carcinoma. , 1993, Cancer research.

[5]  M. Chen,et al.  Interleukin‐10 production by human carcinoma cell lines and its relationship to interleukin‐6 expression , 1993, International journal of cancer.

[6]  Mohamed,et al.  Interleukin 10 production correlates with pathology in human Leishmania donovani infections. , 1993, The Journal of clinical investigation.

[7]  G. Tosato,et al.  Human interleukin-10 can directly inhibit T-cell growth. , 1993, Blood.

[8]  M. de Carli,et al.  Human IL-10 is produced by both type 1 helper (Th1) and type 2 helper (Th2) T cell clones and inhibits their antigen-specific proliferation and cytokine production. , 1993, Journal of immunology.

[9]  D. Longo,et al.  Alterations in signal transduction molecules in T lymphocytes from tumor-bearing mice. , 1992, Science.

[10]  J. Berek,et al.  Presence of interleukin 10 (IL-10) in the ascites of patients with ovarian and other intra-abdominal cancers. , 1992, Cytokine.

[11]  E. Halapi,et al.  Selective expression of interleukin 10, interferon gamma, and granulocyte-macrophage colony-stimulating factor in ovarian cancer biopsies. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[12]  T. Whiteside,et al.  Expression of mRNA for cytokines in tumor‐infiltrating mononuclear cells in ovarian adenocarcinoma and invasive breast cancer , 1992, International journal of cancer.

[13]  H. Spits,et al.  Differential effects of IL-4 and IL-10 on IL-2-induced IFN-gamma synthesis and lymphokine-activated killer activity. , 1992, International immunology.

[14]  A. Sher,et al.  IL-10 inhibits parasite killing and nitrogen oxide production by IFN-gamma-activated macrophages. , 1992, Journal of immunology.

[15]  M. Howard,et al.  Ly‐1 B (B‐1) cells are the main source of B cell‐derived interleukin 10 , 1992, European journal of immunology.

[16]  U. Reinhold,et al.  Tumor‐infiltrating lymphocytes isolated from a Ki‐1–positive large cell lymphoma of the skin. Phenotypic characterization and analysis of cytokine secretion , 1991, Cancer.

[17]  J. Convit,et al.  Differing lymphokine profiles of functional subsets of human CD4 and CD8 T cell clones. , 1991, Science.

[18]  C. Figdor,et al.  Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression , 1991, The Journal of experimental medicine.

[19]  N. Chakraborty,et al.  Suppression of lymphokine-activated killer cell generation by tumor-infiltrating lymphocytes. , 1991, Clinical immunology and immunopathology.

[20]  T. Mosmann,et al.  The role of IL-10 in crossregulation of TH1 and TH2 responses. , 1991, Immunology today.

[21]  S. Miescher,et al.  Clonal and frequency analyses of tumor-infiltrating T lymphocytes from human solid tumors. , 1987, Journal of immunology.

[22]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[23]  A. Chang,et al.  Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. , 1985, The New England journal of medicine.

[24]  J. Svennevig,et al.  Lymphoid infiltration and prognosis in colorectal carcinoma. , 1984, British Journal of Cancer.

[25]  S. Poppema,et al.  Insitu analysis of the mononuclear cell infiltrate in primary malignant-melanoma of the skin , 1983 .