Prognostic Value of the CD4+/CD8+ Ratio of Tumour Infiltrating Lymphocytes in Colorectal Cancer and HLA-DR Expression on Tumour Cells

Overview

Journal Cancer Immunol Immunother

Specialties Allergy & Immunology
Oncology
Pharmacology

Date 2003 Apr 16

PMID 12695859

Citations 113

Authors

Axel C P Diederichsen

J V B Hjelmborg

Per B Christensen

Jesper Zeuthen

Claus Fenger

Affiliations

Soon will be listed here.

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.

Citing Articles

PPIH is a novel diagnostic biomarker associated with immune infiltration in cholangiocarcinoma.

Ye J, Chen Z, Zhang C, Xie R, Chen H, Ren P BMC Cancer. 2025; 25(1):218.

PMID: 39920663 PMC: 11806719. DOI: 10.1186/s12885-025-13607-0.

DNA Methylation in Colorectal Cancer as Potential Prognostic and Predictive Markers.

Zhou R, Li L, Ou Q, Wang Y, Fang Y, Zhang C Biomolecules. 2025; 15(1).

PMID: 39858498 PMC: 11763947. DOI: 10.3390/biom15010104.

Tumor-Infiltrating Immune Cells in Colorectal Cancer.

Ferkel S, Holman E, Sojwal R, Rubin S, Rogalla S Neoplasia. 2024; 59:101091.

PMID: 39642846 PMC: 11665540. DOI: 10.1016/j.neo.2024.101091.

Single-cell spatial mapping reveals alteration of cell type composition and tissue microenvironment during early colorectal cancer formation.

Guha T, Esplin E, Horning A, Chiu R, Paul K, Weimer A bioRxiv. 2024; .

PMID: 39605357 PMC: 11601668. DOI: 10.1101/2024.11.20.622725.

Spatial Profiling of Ovarian Carcinoma and Tumor Microenvironment Evolution under Neoadjuvant Chemotherapy.

Yaniz-Galende E, Zeng Q, Bejar-Grau J, Klein C, Blanc-Durand F, Le Formal A Clin Cancer Res. 2024; 30(13):2790-2800.

PMID: 38669064 PMC: 11215404. DOI: 10.1158/1078-0432.CCR-23-3836.

References

Dukes C, Bussey H . The spread of rectal cancer and its effect on prognosis. Br J Cancer. 1958; 12(3):309-20. PMC: 2073915. DOI: 10.1038/bjc.1958.37. View

Ostenstad B, Lea T, Schlichting E, HARBOE M . Human colorectal tumour infiltrating lymphocytes express activation markers and the CD45RO molecule, showing a primed population of lymphocytes in the tumour area. Gut. 1994; 35(3):382-7. PMC: 1374595. DOI: 10.1136/gut.35.3.382. View

Lengauer C, Kinzler K, Vogelstein B . Genetic instability in colorectal cancers. Nature. 1997; 386(6625):623-7. DOI: 10.1038/386623a0. View

Garrido F, Cabrera T, Lopez-Nevot M, Ruiz-Cabello F . HLA class I antigens in human tumors. Adv Cancer Res. 1995; 67:155-95. DOI: 10.1016/s0065-230x(08)60713-7. View

Matsuda S, Yamane T, Hamaji M . CD4- and TCRalphabeta-positive T lymphocytes predominantly infiltrated into well-moderately differentiated colon adenocarcinoma tissues. Jpn J Clin Oncol. 1998; 28(2):97-103. DOI: 10.1093/jjco/28.2.97. View

Moore M, Ghosh A, Jones D . MHC status of primary human colorectal carcinoma: biological significance and implications for host immune recognition. Acta Chir Scand Suppl. 1989; 549:17-25. View

Naito Y, Saito K, Shiiba K, Ohuchi A, Saigenji K, Nagura H . CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer. Cancer Res. 1998; 58(16):3491-4. View

Di Giorgio A, Botti C, Tocchi A, Mingazzini P, FLAMMIA M . The influence of tumor lymphocytic infiltration on long term survival of surgically treated colorectal cancer patients. Int Surg. 1992; 77(4):256-60. View

Diederichsen A, Zeuthen J, Christensen P, Kristensen T . Characterisation of tumour infiltrating lymphocytes and correlations with immunological surface molecules in colorectal cancer. Eur J Cancer. 1999; 35(5):721-6. DOI: 10.1016/s0959-8049(99)00033-7. View

10.

Banner B, Savas L, Baker S, Woda B . Characterization of the inflammatory cell populations in normal colon and colonic carcinomas. Virchows Arch B Cell Pathol Incl Mol Pathol. 1993; 64(4):213-20. DOI: 10.1007/BF02915115. View

11.

Moller P, Momburg F, Koretz K, Moldenhauer G, Herfarth C, Otto H . Influence of major histocompatibility complex class I and II antigens on survival in colorectal carcinoma. Cancer Res. 1991; 51(2):729-36. View

12.

Matsuda M, Petersson M, Lenkei R, Taupin J, Magnusson I, Mellstedt H . 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. 1995; 61(6):765-72. DOI: 10.1002/ijc.2910610605. View

13.

Bodmer W, Browning M, Krausa P, Rowan A, Bicknell D, Bodmer J . Tumor escape from immune response by variation in HLA expression and other mechanisms. Ann N Y Acad Sci. 1993; 690:42-9. DOI: 10.1111/j.1749-6632.1993.tb43994.x. View

14.

Andersen S, Rognum T, Lund E, Meling G, Hauge S . Strong HLA-DR expression in large bowel carcinomas is associated with good prognosis. Br J Cancer. 1993; 68(1):80-5. PMC: 1968312. DOI: 10.1038/bjc.1993.290. View

15.

Guidoboni M, Gafa R, Viel A, Doglioni C, Russo A, Santini A . Microsatellite instability and high content of activated cytotoxic lymphocytes identify colon cancer patients with a favorable prognosis. Am J Pathol. 2001; 159(1):297-304. PMC: 1850401. DOI: 10.1016/S0002-9440(10)61695-1. View

16.

Kaklamanis L, Gatter K, Hill A, Mortensen N, Harris A, Krausa P . Loss of HLA class-I alleles, heavy chains and beta 2-microglobulin in colorectal cancer. Int J Cancer. 1992; 51(3):379-85. DOI: 10.1002/ijc.2910510308. View

17.

Diederichsen A, Hansen T, Nielsen O, Fenger C, Jensenius J, Christensen P . A comparison of flow cytometry and immunohistochemistry in human colorectal cancers. APMIS. 1998; 106(5):562-70. DOI: 10.1111/j.1699-0463.1998.tb01385.x. View

18.

Lazaris A, Theodoropoulos G, Davaris P, Panoussopoulos D, Nakopoulou L, Kittas C . Heat shock protein 70 and HLA-DR molecules tissue expression. Prognostic implications in colorectal cancer. Dis Colon Rectum. 1995; 38(7):739-45. DOI: 10.1007/BF02048033. View

19.

Jass J, Love S, Northover J . A new prognostic classification of rectal cancer. Lancet. 1987; 1(8545):1303-6. DOI: 10.1016/s0140-6736(87)90552-6. View

20.

Csiba A, Whitwell H, Moore M . Distribution of histocompatibility and leucocyte differentiation antigens in normal human colon and in benign and malignant colonic neoplasms. Br J Cancer. 1984; 50(5):699-709. PMC: 1976977. DOI: 10.1038/bjc.1984.239. View