Skip to main content
Top
Published in: Cancer Immunology, Immunotherapy 7/2003

01-07-2003 | Original Article

Prognostic value of the CD4+/CD8+ ratio of tumour infiltrating lymphocytes in colorectal cancer and HLA-DR expression on tumour cells

Authors: Axel C. P. Diederichsen, J. v. B. Hjelmborg, Per B. Christensen, Jesper Zeuthen, Claus Fenger

Published in: Cancer Immunology, Immunotherapy | Issue 7/2003

Login to get access

Abstract

The purpose of this study was to clarify whether HLA-DR expression of colorectal tumour cells or the CD4+/CD8+ ratio of the tumour infiltrating lymphocytes is significantly associated with the prognosis of colorectal cancer. Using flow cytometry, we studied the tumour cell expression of the HLA class II in 70 enzymatically dissociated colorectal cancers and the phenotype of tumour infiltrating lymphocytes (TILs) in 41 cases. There was no trend in 5-year survival between three levels (low, medium, high) of HLA-DR expression on the tumour cells. Patients with low CD4+/CD8+ ratios had a better clinical course, with significantly higher 5-year survival, p=0.046, independent of the Dukes stage and age. Our results have implications for tumour immunology; colorectal cancer cells might be a target for cytotoxic T-lymphocytes, however the tumour cells are not able to initiate an immune response. Stimulation of the immune system could possible be obtained using dendritic cells cultured in vitro and loaded with tumour antigens.
Literature
1.
go back to reference Andersen SN, Rognum TO, Lund E, Meling GI, Hauge S (1993) Strong HLA-DR expression in large bowel carcinomas is associated with good prognosis. Br J Cancer 68:80PubMed Andersen SN, Rognum TO, Lund E, Meling GI, Hauge S (1993) Strong HLA-DR expression in large bowel carcinomas is associated with good prognosis. Br J Cancer 68:80PubMed
2.
go back to reference Banner BF, Savas L, Baker S, Woda BA (1993) Characterization of the inflammatory cell populations in normal colon and colonic carcinomas. Virchows Arch B Cell Pathol Incl Mol Pathol 64:213PubMed Banner BF, Savas L, Baker S, Woda BA (1993) Characterization of the inflammatory cell populations in normal colon and colonic carcinomas. Virchows Arch B Cell Pathol Incl Mol Pathol 64:213PubMed
3.
go back to reference Bodmer WF, Browning MJ, Krausa P, Rowan A, Bicknell DC, Bodmer JG (1993) Tumor escape from immune response by variation in HLA expression and other mechanisms. Ann N Y Acad Sci 690:42PubMed Bodmer WF, Browning MJ, Krausa P, Rowan A, Bicknell DC, Bodmer JG (1993) Tumor escape from immune response by variation in HLA expression and other mechanisms. Ann N Y Acad Sci 690:42PubMed
4.
go back to reference Csiba A, Whitwell HL, Moore M (1984) Distribution of histocompatibility and leucocyte differentiation antigens in normal human colon and in benign and malignant colonic neoplasms. Br J Cancer 50:699PubMed Csiba A, Whitwell HL, Moore M (1984) Distribution of histocompatibility and leucocyte differentiation antigens in normal human colon and in benign and malignant colonic neoplasms. Br J Cancer 50:699PubMed
5.
go back to reference Di Giorgio A, Botti C, Tocchi A, Mingazzini P, Flammia M (1992) The influence of tumor lymphocytic infiltration on long term survival of surgically treated colorectal cancer patients. Int Surg 77:256PubMed Di Giorgio A, Botti C, Tocchi A, Mingazzini P, Flammia M (1992) The influence of tumor lymphocytic infiltration on long term survival of surgically treated colorectal cancer patients. Int Surg 77:256PubMed
6.
go back to reference Diederichsen ACP, Hansen TP, Nielsen O, Fenger C, Jensenius JC, Christensen PB, Kristensen T, Zeuthen J (1998) A comparison of flow cytometry and immunohistochemistry in human colorectal cancers. APMIS 106:562PubMed Diederichsen ACP, Hansen TP, Nielsen O, Fenger C, Jensenius JC, Christensen PB, Kristensen T, Zeuthen J (1998) A comparison of flow cytometry and immunohistochemistry in human colorectal cancers. APMIS 106:562PubMed
7.
go back to reference Diederichsen ACP, Stenholm ACO, Kronborg O, Fenger C, Jensenius JC, Zeuthen J, Christensen PB, Kristensen T (1998) Flow cytometric investigation of immune-response-related surface molecules on human colorectal cancers. Int J Cancer (Pred Oncol) 79:283 Diederichsen ACP, Stenholm ACO, Kronborg O, Fenger C, Jensenius JC, Zeuthen J, Christensen PB, Kristensen T (1998) Flow cytometric investigation of immune-response-related surface molecules on human colorectal cancers. Int J Cancer (Pred Oncol) 79:283
8.
go back to reference Diederichsen ACP, Zeuthen J, Christensen PB, Kristensen T (1999) Characterisation of tumour infiltrating lymphocytes and correlations with immunological surface molecules in colorectal cancer. Eur J Cancer 35:721CrossRefPubMed Diederichsen ACP, Zeuthen J, Christensen PB, Kristensen T (1999) Characterisation of tumour infiltrating lymphocytes and correlations with immunological surface molecules in colorectal cancer. Eur J Cancer 35:721CrossRefPubMed
9.
go back to reference Dukes CE, Bussey HJR (1958) The spread of rectal cancer and its effect on prognosis. Br J Cancer 12:309 Dukes CE, Bussey HJR (1958) The spread of rectal cancer and its effect on prognosis. Br J Cancer 12:309
10.
go back to reference Garrido F, Cabrera T, Lopez Nevot MA, Ruiz Cabello F (1995) HLA class I antigens in human tumors. Adv Cancer Res 67:155PubMed Garrido F, Cabrera T, Lopez Nevot MA, Ruiz Cabello F (1995) HLA class I antigens in human tumors. Adv Cancer Res 67:155PubMed
11.
go back to reference Guidoboni M, Gafa R, Viel A et al. (2001) Microsatellite instability and high content of activated cytotoxic lymphocytes identify colon cancer patients with a favorable prognosis. Am J Pathol 159:297PubMed Guidoboni M, Gafa R, Viel A et al. (2001) Microsatellite instability and high content of activated cytotoxic lymphocytes identify colon cancer patients with a favorable prognosis. Am J Pathol 159:297PubMed
12.
go back to reference Hÿkansson L, Adell G, Boeryd B, Sjÿgren F, Sjÿdahl R (1997) Infiltration of mononuclear inflammatory cells into primary colorectal carcinomas: an immunohistological analysis. Br J Cancer 75:374PubMed Hÿkansson L, Adell G, Boeryd B, Sjÿgren F, Sjÿdahl R (1997) Infiltration of mononuclear inflammatory cells into primary colorectal carcinomas: an immunohistological analysis. Br J Cancer 75:374PubMed
13.
go back to reference Jass JR, Love SB, Northover JM (1987) A new prognostic classification of rectal cancer. Lancet 1:1303PubMed Jass JR, Love SB, Northover JM (1987) A new prognostic classification of rectal cancer. Lancet 1:1303PubMed
14.
go back to reference Kaklamanis L, Gatter KC, Hill AB, Mortensen N, Harris AL, Krausa P, McMichael A, Bodmer JG, Bodmer WF (1992) Loss of HLA class-I alleles, heavy chains and beta 2-microglobulin in colorectal cancer. Int J Cancer 51:379PubMed Kaklamanis L, Gatter KC, Hill AB, Mortensen N, Harris AL, Krausa P, McMichael A, Bodmer JG, Bodmer WF (1992) Loss of HLA class-I alleles, heavy chains and beta 2-microglobulin in colorectal cancer. Int J Cancer 51:379PubMed
15.
go back to reference Lazaris AC, Theodoropoulos GE, Davaris PS, Panoussopoulos D, Nakopoulou L, Kittas C, Golematis BC (1995) Heat shock protein 70 and HLA-DR molecules tissue expression. Prognostic implications in colorectal cancer. Dis Colon Rectum 38:739PubMed Lazaris AC, Theodoropoulos GE, Davaris PS, Panoussopoulos D, Nakopoulou L, Kittas C, Golematis BC (1995) Heat shock protein 70 and HLA-DR molecules tissue expression. Prognostic implications in colorectal cancer. Dis Colon Rectum 38:739PubMed
16.
go back to reference Lengauer C, Kinzler WK, Vogelstein B (1997) Genetic instability in colorectal cancers. Nature 386:623PubMed Lengauer C, Kinzler WK, Vogelstein B (1997) Genetic instability in colorectal cancers. Nature 386:623PubMed
17.
go back to reference Matsuda M, Petersson M, Lenkei R, Taupin JL, Magnusson I, Mellstedt H, Anderson P, Kiessling R (1995) Alterations in the signal-transducing molecules of T cells and NK cells in colorectal tumor-infiltrating, gut mucosal and peripheral lymphocytes: correlation with the stage of the disease. Int J Cancer 61:765PubMed Matsuda M, Petersson M, Lenkei R, Taupin JL, Magnusson I, Mellstedt H, Anderson P, Kiessling R (1995) Alterations in the signal-transducing molecules of T cells and NK cells in colorectal tumor-infiltrating, gut mucosal and peripheral lymphocytes: correlation with the stage of the disease. Int J Cancer 61:765PubMed
18.
go back to reference Matsuda S, Yamane T, Hamaji M (1998) CD4 and TCR alphabeta-positive T lymphocytes predominantly infiltrated into well-moderately differentiated colon adenocarcinoma tissues. Jpn J Clin Oncol 28:97CrossRefPubMed Matsuda S, Yamane T, Hamaji M (1998) CD4 and TCR alphabeta-positive T lymphocytes predominantly infiltrated into well-moderately differentiated colon adenocarcinoma tissues. Jpn J Clin Oncol 28:97CrossRefPubMed
19.
go back to reference Möller P, Momburg F, Koretz K, Moldenhauer G, Herfarth C, Otto HF, Hammerling GJ, Schlag P (1991) Influence of major histocompatibility complex class I and II antigens on survival in colorectal carcinoma. Cancer Res 51:729PubMed Möller P, Momburg F, Koretz K, Moldenhauer G, Herfarth C, Otto HF, Hammerling GJ, Schlag P (1991) Influence of major histocompatibility complex class I and II antigens on survival in colorectal carcinoma. Cancer Res 51:729PubMed
20.
go back to reference Moore M, Ghosh AK, Jones DJ (1989) MHC status of primary human colorectal carcinoma: biological significance and implications for host immune recognition. Acta Chir Scand Suppl 549:17PubMed Moore M, Ghosh AK, Jones DJ (1989) MHC status of primary human colorectal carcinoma: biological significance and implications for host immune recognition. Acta Chir Scand Suppl 549:17PubMed
21.
go back to reference Naito Y, Saito K, Shiiba K, Ohuchi A, Saigenji K, Nagura H, Ohtani H (1998) CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer. Cancer Res 58:3491PubMed Naito Y, Saito K, Shiiba K, Ohuchi A, Saigenji K, Nagura H, Ohtani H (1998) CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer. Cancer Res 58:3491PubMed
22.
go back to reference Østenstad B, Lea T, Schlichting E, Harboe M (1994) Human colorectal tumour infiltrating lymphocytes express activation markers and the CD45RO molecule, showing a primed population of lymphocytes in the tumour area. Gut 35:382PubMed Østenstad B, Lea T, Schlichting E, Harboe M (1994) Human colorectal tumour infiltrating lymphocytes express activation markers and the CD45RO molecule, showing a primed population of lymphocytes in the tumour area. Gut 35:382PubMed
23.
go back to reference Schwartz RH (1990) A cell culture model for T lymphocyte clonal anergy. Science 248:1349PubMed Schwartz RH (1990) A cell culture model for T lymphocyte clonal anergy. Science 248:1349PubMed
24.
go back to reference Turnbull RB Jr, Kyle K, Watson FR, Spratt J (1967) Cancer of the colon: the influence of the no-touch isolation technic on survival rates. Ann Surg 166:420PubMed Turnbull RB Jr, Kyle K, Watson FR, Spratt J (1967) Cancer of the colon: the influence of the no-touch isolation technic on survival rates. Ann Surg 166:420PubMed
Metadata
Title
Prognostic value of the CD4+/CD8+ ratio of tumour infiltrating lymphocytes in colorectal cancer and HLA-DR expression on tumour cells
Authors
Axel C. P. Diederichsen
J. v. B. Hjelmborg
Per B. Christensen
Jesper Zeuthen
Claus Fenger
Publication date
01-07-2003
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 7/2003
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-003-0388-5

Other articles of this Issue 7/2003

Cancer Immunology, Immunotherapy 7/2003 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine