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. 2000 Feb 1;82(5):1009–1012. doi: 10.1054/bjoc.1999.1034

Reduction in cytokine production in colorectal cancer patients: association with stage and reversal by resection

A G Heriot 1,#, J B Marriott 2,#, S Cookson 2, D Kumar 1, A G Dalgleish 2
PMCID: PMC2374422  PMID: 10737381

Abstract

The aim of this study was to assess monocyte/macrophage function, as defined by lipopolysaccharide (LPS)-induced production of tumour necrosis factor (TNF)-α, interleukin (IL)-10 and interferon (IFN)-γ by stimulated whole blood cultures in patients with colorectal carcinoma before and after surgical resection. Forty colorectal cancer patients prior to surgery and 31 healthy controls were studied. Heparinized venous blood was taken from colorectal cancer patients prior to surgery and from healthy controls. Serial samples were obtained at least 3–6 weeks post-operatively. Blood was stimulated with LPS for 24 h and supernatants were assayed for TNF-α, IFN-γ and IL-10 by enzyme-linked immunosorbent assay. LPS-induced production of TNF-α and of IFN-γ was reduced in patients with colorectal carcinoma compared to controls (TNF-α, 11 269 pg ml−1{12 598}; IFN-γ, 0.00 pg ml−1{226}; median {IQR}) (TNF-α, 20 576 pg ml−1{11 637}, P< 0.0001; IFN-γ, 1048 {2428}, P = 0.0051, Mann–Whitney U -test). Production in patients after surgery had increased (TNF-α: 17 620 pg ml−1{7986}; IFN-γ: 410 pg ml−1{2696}; mean {s.d.}) and were no longer significantly reduced when compared to controls (TNF-α, P = 0.28; IFN-γ, P = 0.76). Production of TNF-α and IFN-γ prior to surgery were reduced to a greater extent in patients with Dukes' stage C tumours compared to those with Dukes' stage A and B stage. There was no difference in IL-10 production between any group. Monocytes/macrophages from patients with colorectal carcinoma are refractory to LPS stimulation as reflected by reduction in TNF-α and IFN-γ production and this is more pronounced in patients with advanced stage tumours. This suppression is not mediated by IL-10 and disappears following surgical resection of the tumour. This provides evidence for tumour induced suppression of immune function in patients with colorectal cancer and identifies a potential therapeutic avenue. © 2000 Cancer Research Campaign

Keywords: colorectal cancer, cytokines, immune suppression

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Footnotes

This work has been presented as an abstract at the British Society of Gastroenterology, Harrogate, March 1998, and the Digestive Diseases Week, New Orleans, May 1998.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arista M. C., Callopoli A., De Franceschi L., Santini A., Schiratti M., Conti L., Di Filippo F., Gandolfo G. M. Flow cytometric study of lymphocyte subsets in patients at different stages of colorectal carcinoma. Dis Colon Rectum. 1994 Feb;37(2 Suppl):S30–S34. doi: 10.1007/BF02048428. [DOI] [PubMed] [Google Scholar]
  2. Barni S., Lissoni P., Cazzaniga M., Ardizzoia A., Meregalli S., Fossati V., Fumagalli L., Brivio F., Tancini G. A randomized study of low-dose subcutaneous interleukin-2 plus melatonin versus supportive care alone in metastatic colorectal cancer patients progressing under 5-fluorouracil and folates. Oncology. 1995 May-Jun;52(3):243–245. doi: 10.1159/000227465. [DOI] [PubMed] [Google Scholar]
  3. Brivio F., Lissoni P., Alderi G., Barni S., Lavorato F., Fumagalli L. Preoperative interleukin-2 subcutaneous immunotherapy may prolong the survival time in advanced colorectal cancer patients. Oncology. 1996 Jul-Aug;53(4):263–268. doi: 10.1159/000227571. [DOI] [PubMed] [Google Scholar]
  4. Cole W. H., Humphrey L. Need for immunologic stimulators during immunosuppression produced by major cancer surgery. Ann Surg. 1985 Jul;202(1):9–20. doi: 10.1097/00000658-198507000-00002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Darcy P. K., Kershaw M. H., Trapani J. A., Smyth M. J. Expression in cytotoxic T lymphocytes of a single-chain anti-carcinoembryonic antigen antibody. Redirected Fas ligand-mediated lysis of colon carcinoma. Eur J Immunol. 1998 May;28(5):1663–1672. doi: 10.1002/(SICI)1521-4141(199805)28:05<1663::AID-IMMU1663>3.0.CO;2-L. [DOI] [PubMed] [Google Scholar]
  6. Elsässer-Beile U., von Kleist S., Fischer R., Mönting J. S. Impaired cytokine production in whole blood cell cultures from patients with colorectal carcinomas as compared to benign colorectal tumors and controls. J Clin Lab Anal. 1992;6(5):311–314. doi: 10.1002/jcla.1860060510. [DOI] [PubMed] [Google Scholar]
  7. Hammer J. H., Nielsen H. J., Moesgaard F., Kehlet H. Duration of postoperative immunosuppression assessed by repeated delayed type hypersensitivity skin tests. Eur Surg Res. 1992;24(3):133–137. doi: 10.1159/000129199. [DOI] [PubMed] [Google Scholar]
  8. Hrouda D., Muir G. H., Dalgleish A. G. The role of immunotherapy for urological tumours. Br J Urol. 1997 Mar;79(3):307–316. doi: 10.1046/j.1464-410x.1997.00301.x. [DOI] [PubMed] [Google Scholar]
  9. King J., Caplehorn J. R., Ross W. B., Morris D. L. High serum carcinoembryonic antigen concentration in patients with colorectal liver metastases is associated with poor cell-mediated immunity, which is predictive of survival. Br J Surg. 1997 Oct;84(10):1382–1385. [PubMed] [Google Scholar]
  10. McMillan D. C., Fyffe G. D., Wotherspoon H. A., Cooke T. G., McArdle C. S. Prospective study of circulating T-lymphocyte subpopulations and disease progression in colorectal cancer. Dis Colon Rectum. 1997 Sep;40(9):1068–1071. doi: 10.1007/BF02050931. [DOI] [PubMed] [Google Scholar]
  11. Mittelman A., Huberman M., Puccio C., Fallon B., Tessitore J., Savona S., Eyre R., Gafney E., Wick M., Skelos A. A phase I study of recombinant human interleukin-2 and alpha-interferon-2a in patients with renal cell cancer, colorectal cancer, and malignant melanoma. Cancer. 1990 Aug 15;66(4):664–669. doi: 10.1002/1097-0142(19900815)66:4<664::aid-cncr2820660411>3.0.co;2-d. [DOI] [PubMed] [Google Scholar]
  12. O'Hara R. J., Greenman J., Drew P. J., McDonald A. W., Duthie G. S., Lee P. W., Monson J. R. Impaired interleukin-12 production is associated with a defective anti-tumor response in colorectal cancer. Dis Colon Rectum. 1998 Apr;41(4):460–463. doi: 10.1007/BF02235759. [DOI] [PubMed] [Google Scholar]
  13. Pullyblank A. M., Guillou P. J., Monson J. R. Interleukin 1 and tumour necrosis factor alpha may be responsible for the lytic mechanism during anti-tumour antibody-dependent cell-mediated cytotoxicity. Br J Cancer. 1995 Sep;72(3):601–606. doi: 10.1038/bjc.1995.380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Riethmüller G., Schneider-Gädicke E., Schlimok G., Schmiegel W., Raab R., Höffken K., Gruber R., Pichlmaier H., Hirche H., Pichlmayr R. Randomised trial of monoclonal antibody for adjuvant therapy of resected Dukes' C colorectal carcinoma. German Cancer Aid 17-1A Study Group. Lancet. 1994 May 14;343(8907):1177–1183. doi: 10.1016/s0140-6736(94)92398-1. [DOI] [PubMed] [Google Scholar]
  15. Tancini G., Barni S., Rescaldani R., Fiorelli G., Vivani S., Lissoni P. Analysis of T helper and suppressor lymphocyte subsets in relation to the clinical stage of solid neoplasms. Oncology. 1990;47(5):381–384. doi: 10.1159/000226852. [DOI] [PubMed] [Google Scholar]
  16. Tsutsui S., Morita M., Kuwano H., Matsuda H., Mori M., Okamura S., Sugimachi K. Influence of preoperative treatment and surgical operation on immune function of patients with esophageal carcinoma. J Surg Oncol. 1992 Mar;49(3):176–181. doi: 10.1002/jso.2930490310. [DOI] [PubMed] [Google Scholar]

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