Loss of tissue expression of interleukin-10 promotes the disease progression of colorectal carcinoma

PurposeInterleukin-10 (IL-10) is a unique cytokine that is thought to be a potent immunostimulatory and immunosuppressive factor. The aim of this study was to investigate IL-10 expression in colorectal cancer, and clarify its relationship to the clinicopathological findings and prognosis.MethodsTissue samples were collected from 92 patients with colorectal cancer and adjacent normal mucosa. The expression of IL-10 in colorectal cancer tissues was evaluated by immunohistochemistry. Tissue levels of IL-10 were measured by enzyme-linked immunosorbent assay.ResultsThe mean concentration of IL-10 did not significantly differ between the cancer tissue and adjacent normal mucosa. The IL-10 concentration in cancer tissue with positive staining immunohistochemically was significantly higher than that without IL-10 staining. The IL-10 level in cancer tissue decreased in accordance with advanced-stage serosal invasion and lymph node involvement, and thus predicted poor survival in patients undergoing surgery with curative intent. A Cox multivariate analysis demonstrated that a decreased IL-10 level in cancer tissue was an independent risk factor for poor survival.ConclusionThe tumor IL-10 level in colorectal cancer was inversely correlated with serosal invasion and lymph node metastasis, which thus reflected tumor progression. Evaluating the tumor expression of IL-10 may therefore provide valuable information for predicting the long-term survival in patients undergoing surgery with curative intent.

[1]  A. Ganser,et al.  ©1999 Cancer Research Campaign Article no. bjoc.1998.0189 , 2022 .

[2]  R. Dummer,et al.  Interleukin‐10 is a growth factor for human melanoma cells and down‐regulates HLA class‐I, HLA class‐II and ICAM‐1 molecules , 1997, International journal of cancer.

[3]  M. Björkholm,et al.  Interleukin‐10 mRNA expression in B‐cell chronic lymphocytic leukaemia inversely correlates with progression of disease , 1996, British journal of haematology.

[4]  G. Catalano,et al.  Serum interleukin‐10 levels in patients with advanced gastrointestinal malignancies , 1999, Cancer.

[5]  R. Kurzrock,et al.  Serum levels of interleukin-10 in patients with diffuse large cell lymphoma: lack of correlation with prognosis. , 1995, Blood.

[6]  V. Diehl,et al.  Poor clinical outcome of patients with Hodgkin's Disease and elevated interleukin-10 serum levels , 2000, Annals of Hematology.

[7]  Keith Wilson,et al.  Interleukin‐10 gene transfer inhibits murine mammary tumors and elevates nitric oxide , 1998, International journal of cancer.

[8]  B. Bonavida,et al.  Inhibition of interleukin 10 by rituximab results in down-regulation of bcl-2 and sensitization of B-cell non-Hodgkin's lymphoma to apoptosis. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[9]  Li Mao,et al.  Prognostic factors in resected stage I non-small-cell lung cancer: a multivariate analysis of six molecular markers. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  H. Wanebo,et al.  Interleukin-10 as a possible mediator of immunosuppressive effect in patients with squamous cell carcinoma of the head and neck , 1997, Annals of Surgical Oncology.

[11]  T. Blankenstein,et al.  Interleukin 10 transfected into Chinese hamster ovary cells prevents tumor growth and macrophage infiltration. , 1993, Cancer research.

[12]  G. Pawelec,et al.  T cells and aging. , 1998, Frontiers in bioscience : a journal and virtual library.

[13]  M. Bar‐eli,et al.  Regulation of tumor growth and metastasis by interleukin-10: the melanoma experience. , 1999, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[14]  D. Longo,et al.  Ammonium Trichloro(dioxoethylene-o,o′)tellurate (AS101) Sensitizes Tumors to Chemotherapy by Inhibiting the Tumor Interleukin 10 Autocrine Loop , 2004, Cancer Research.

[15]  C. Franceschi,et al.  T cells and aging, January 2002 update. , 2002, Frontiers in bioscience : a journal and virtual library.

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

[17]  J. Blay,et al.  Interleukin-6, interleukin-10, and vascular endothelial growth factor in metastatic renal cell carcinoma: prognostic value of interleukin-6--from the Groupe Francais d'Immunotherapie. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[18]  M. Caligiuri,et al.  A review of the association between interleukin-10 and human B-cell malignancies , 1998, Cancer Immunology, Immunotherapy.

[19]  J. Rhim,et al.  Role of interleukin 10 and transforming growth factor beta1 in the angiogenesis and metastasis of human prostate primary tumor lines from orthotopic implants in severe combined immunodeficiency mice. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[20]  J. Kim,et al.  IL-10 production in cutaneous basal and squamous cell carcinomas. A mechanism for evading the local T cell immune response. , 1995, Journal of immunology.

[21]  R. Kurzrock,et al.  Cytokines in pancreatic carcinoma , 2004, Cancer.

[22]  Y. Mohri,et al.  Perioperative host-tumor inflammatory interactions: A potential trigger for disease recurrence following a curative resection for colorectal cancer , 2008, Surgery Today.

[23]  E. Maxwell,et al.  Interleukin-10 inhibits tumor metastasis through an NK cell-dependent mechanism , 1996, The Journal of experimental medicine.

[24]  L. Lin,et al.  IL-10, T lymphocyte inhibitor of human blood cell production of IL-1 and tumor necrosis factor. , 1992, Journal of immunology.

[25]  G. Catalano,et al.  Serum interleukin-10 levels as a prognostic factor in advanced non-small cell lung cancer patients. , 2000, Chest.

[26]  C. Grunfeld.  Leptin and the immunosuppression of malnutrition. , 2002, The Journal of clinical endocrinology and metabolism.

[27]  G. Salles,et al.  Interleukin-10 gene promoter polymorphisms influence the clinical outcome of diffuse large B-cell lymphoma. , 2004, Blood.

[28]  M. Goldman,et al.  Loss of tumorigenicity and increased immunogenicity induced by interleukin-10 gene transfer in B16 melanoma cells. , 1996, Human gene therapy.

[29]  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.

[30]  K. Asadullah,et al.  Interleukin-10 Therapy—Review of a New Approach , 2003, Pharmacological Reviews.

[31]  M. Lotze,et al.  Systemic administration of cellular IL-10 induces an effective, specific, and long-lived immune response against established tumors in mice. , 1996, Journal of immunology.

[32]  A. Dalgleish,et al.  Reduction in cytokine production in colorectal cancer patients: association with stage and reversal by resection , 2000, British Journal of Cancer.

[33]  M. Jourdan,et al.  Interleukin-10 and Gp130 cytokines in human multiple myeloma. , 1999, Leukemia & lymphoma.

[34]  P. Musiani,et al.  Local release of IL-10 by transfected mouse mammary adenocarcinoma cells does not suppress but enhances antitumor reaction and elicits a strong cytotoxic lymphocyte and antibody-dependent immune memory. , 1995, Journal of immunology.

[35]  C. Chi,et al.  Serum interleukin-10 but not interleukin-6 is related to clinical outcome in patients with resectable hepatocellular carcinoma. , 2000, Annals of surgery.

[36]  J. Nemunaitis,et al.  Comparison of Serum Interleukin-10 (IL-10) Levels Between Normal Volunteers and Patients with Advanced Melanoma , 2001, Cancer investigation.

[37]  Weiping Zou,et al.  Immunosuppressive networks in the tumour environment and their therapeutic relevance , 2005, Nature Reviews Cancer.

[38]  L. Pelosio,et al.  Prognostic significance of circulating IL-10 and IL-6 serum levels in colon cancer patients undergoing surgery. , 2002, Clinical immunology.

[39]  M. Ledda,et al.  IL-10 expression by CT26 colon carcinoma cells inhibits their malignant phenotype and induces a T cell-mediated tumor rejection in the context of a systemic Th2 response , 1999, Gene Therapy.

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

[41]  G. Catalano,et al.  Circulating levels of interleukin-10 and interleukin-6 in gastric and colon cancer patients before and after surgery: relationship with radicality and outcome. , 2002, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[42]  J. Herbeuval,et al.  Recruitment of STAT3 for Production of IL-10 by Colon Carcinoma Cells Induced by Macrophage-Derived IL-61 , 2004, The Journal of Immunology.

[43]  J. Becker,et al.  Elevated serum levels of interleukin-10 in patients with metastatic malignant melanoma. , 1995, Melanoma research.

[44]  W. Gianni,et al.  Persistence of epidermal growth factor receptor and interleukin 10 in blood of colorectal cancer patients after surgery identifies patients with high risk to relapse. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[45]  H. Granger,et al.  Abolished angiogenicity and tumorigenicity of Burkitt lymphoma by interleukin-10. , 2000, Blood.

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

[47]  M. Denis,et al.  Mucosal IL-10 and TGF-beta play crucial roles in preventing LPS-driven, IFN-gamma-mediated epithelial damage in human colon explants. , 2008, The Journal of clinical investigation.