Infiltration of mononuclear inflammatory cells into primary colorectal carcinomas: an immunohistological analysis

Abstract

Infiltration of mononuclear inflammatory cells into primary colorectal carcinomas: an immunohistological analysis L HAkansson1, G Adell1, B Boeryd2, F Sjogren3 and R Sjodahl4Departments of 'Oncology, 2Pathology, 3Clinical Immunology and 4Surgery, University Hospital of Linkoping, S-581 85 Linkoping, Sweden Summary 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 CD1 1 c+ 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 Il-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 tumourinfiltrating 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.

Effects of cytokine-induced macrophages on the response of tumor cells to banoxantrone (AQ4N)

“…On the other hand, macrophages in stomach cancer were associated with good prognosis of the disease (42), and there has been varying results with lung cancer (43,44). Two studies on 26 and 30 patients, respectively, showed that low infiltration of macrophages correlated with more advanced colorectal cancer (45,46). A recent study indicated that a dense macrophage infiltration at the tumor front positively influenced prognosis in colon cancer (47).…”

NF-kappaB, p38 MAPK and JNK are highly expressed and active in the stroma of human colonic adenomatous polyps

“…Higher numbers of in®ltrating macrophages are associated with more advanced stage in colon cancer (Hakansson et al, 1997) and expression of the growth factor wnt that lies upstream of the APC/Beta Catenin pathway, the major pathway that is mutated in colon cancer, has also been localised to macrophages within the cancer stroma (Smith et al, 1999). The authors of these studies suggest that macrophages may have a paracrine e ect possibly by suppressing the activity of other cytotoxic immune cells, or by the direct e ect of the cytokines they secrete on the epithelial cells.…”

Expression of the macrophage antigen CD163 in rectal cancer cells is associated with early local recurrence and reduced survival time

“…[41][42][43][44] In colorectal cancer, there are conflicting data about the clinical significance of macrophage infiltration. 41,[45][46][47][48][49] In this study, macrophage infiltration was difficult to evaluate because of small tissue cores (0.6 mm in diameter).…”