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.

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In human colorectal cancer it has been reported that some tumours lack the HLA‐ABC antigens. This has been interpreted as reflecting tumour escape from the immune system. Earlier data have been obtained by immunohistochemistry. In this study, we compared the expression of HLA‐ABC, HLA‐DR, CD80 (B7–1) and CD54 (ICAM‐1) in 20 tumours using both a conventional immunohistochemistry two‐layer technique and multiparameter flow cytometry, gating on an epithelial cell marker. Colorectal cancer tissue used in flow cytometry was dissociated with collagenase, deoxyribonuclease and hyaluronidase. The intensity of expression of HLA‐ABC, HLA‐DR and CD80 was unaffected by the enzymes, but CD54 was decreased by 30%. The reproducibility of flow cytometry was good. Microscopy of sections revealed that about 5% of each tumour sample consisted of normal epithelium, but even after correction for this, flow cytometry was superior to immunohistochemistry in 33 out of 80 cases, and showed that tumours described as HLA‐ABC negative by immunohistochemistry were in fact weakly positive for HLA‐ABC. We conclude that flow cytometry and immunohistochemistry are complementary, and that flow cytometry is superior to immunohistochemistry for detecting anti‐gens/epitopes present in low amounts.

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Our purpose was to clarify whether human colorectal cancer cells are equipped to present tumour‐associated‐antigens to the immune system, and whether this ability correlates with lymphoid infiltration, the Dukes' stage and Jass classification. Enzymatically dissociated tumour cells from 70 different colorectal cancers were monitored by multiparameter flow cytometry. Gating on EP4+ cells, the expression of the surface molecules HLA class I, HLA class II, CD80 (B7‐1), CD54 (ICAM‐1) and CD58 (LFA‐3) was evaluated. In 60 of 70 tumours, all tumour cells expressed HLA class I, in 10 tumours 15‐96% of the tumour cells expressed HLA class I. In 1 tumour, all tumour cells expressed HLA class II, in 67 tumours some expressed HLA class II, in 2 tumours none expressed HLA class II. Expression of CD58 was heterogeneous, and there was no or only sparse expression of CD80 and CD54. Expression of the HLA class I molecules, but not the class II, was correlated with lymphoid infiltration and the Jass classification. Expression of these surface molecules was not correlated with the Dukes' stage. The tumour cells were generally equipped to present antigens to the effector arm of the immune system since HLA class I is expressed, but the tumour cells were not optimal in stimulating an immune response, since HLA class II and CD58 were only marginally expressed and CD80 and CD54 were absent. Int. J. Cancer (Pred. Oncol.) 79:283–287, 1998.© 1998 Wiley‐Liss, Inc.