Abstract
Local immunoregulation mediated by mononuclear tumour-infiltrating cells is considered of importance for tumour progression of colorectal cancer, although the balance between immunosuppressor and cytotoxic activities is unclear. Colorectal cancers from 26 patients were investigated using a panel of monoclonal antibodies in order to identify subsets of mononuclear inflammatory cells and to study their pattern of distribution in relation to tumour stage and cytotoxic immune reactivity against the tumour. In all but five tumours, mononuclear cells, lymphocytes or monocytes were present in fairly large numbers, particularly in the stroma. The infiltration of CD4+ mononuclear cells predominated over the CD8+ subset. Infiltration near the tumour cells was found in four cancers only. Stromal infiltration of CD11c+ macrophages was found in all but eight tumours. Small regressive areas, in which the histological architecture of the tumours was broken down, were found in 17 tumours with intense or moderate infiltration by CD4+ lymphocytes or CD11c+ macrophages. Probably this destruction of tumour tissue was caused by cytotoxic activity of the tumour-infiltrating mononuclear cells. In Dukes' class A and B tumours, CD4+ lymphocytes predominated over CD4+ cells with macrophage morphology, but the latter were increasingly found in Dukes' class C and D disease. The occurrence of MHC II-positive macrophages and lymphocytes in different Dukes' classes was similar to that of CD4+ cells. In contrast to this, CD11c+ and CD11a+ cells were more frequent in Dukes' A and B class tumours compared with Dukes' C and D. Four out of nine tumours of the latter stages showed a poor inflammatory reaction. The interpretation of our results is that the subsets of tumour-infiltrating mononuclear cells change with advancing Dukes' class and that the local immune control is gradually broken down in progressive tumour growth, even if some cytotoxic activity is still present.
Highlights
In all tumours except five, lymphocytes or monocytes were present in fairly large numbers, in the stroma
The presence of CD4+ and CD8+ tumour-infiltrating lymphocytes in colorectal cancer has varied in different studies (Csiba et al, 1984; Lennard et al, 1984; Allen and Hogg, 1985; Koch et al, 1985; Umpleby et al, 1985; Ebert et al, 1989)
In agreement with other reports, we found that tumour-infiltrating lymphocytes only occasionally display NK markers (Kornstein et al, 1983; Watanabe et al, 1983; Csiba et al, 1984; Ebert et al, 1989)
Summary
This report includes 22 primary colon and four rectal carcinomas from ten males and 16 females. Median age was 71 years (range 57-84). The number of tumours according to Dukes' classification was: A 3, B 13, C 5 and D 5. The majority of these tumours were moderately well differentiated. All Dukes' A, 2/13 Dukes' B and no Dukes' C tumours were well differentiated and one poorly differentiated tumour was found in each of Dukes' classes B, C and D. The difference in distribution of inflammatory cells between Dukes' stages was analysed using the Fisher's exact test
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