Tumor infiltrating cells in human cancer. On the possible role of CD16+ macrophages in antitumor cytotoxicity.
BACKGROUND
To obtain a better understanding of the mechanism underlying different modalities of immunotherapy, we investigated the types of tumor-infiltrating cells present at the tumor site, with special attention to the presence of macrophages.


METHODS
Frozen sections of carcinomas of the kidney, colon, breast, lung, ovary, and thyroid gland, as well as malignant melanoma were investigated with a panel of monoclonal antibodies against macrophage, T cell and NK cell associated antigens. Both type and pattern of the tumor-infiltrating cells were analyzed.


RESULTS
All tumor-infiltrating cells accumulated preferentially in the stromal bands between tumor cells. In all types of tumor, CD11c+, CD14+, CD68+ and alpha-naphthyl-acetate-esterase positive monocytes/macrophages accounted for most tumor-infiltrating cells. Next in frequency were T lymphocytes (CD2+, CD3+, TCR alpha beta +). Only a few B lymphocytes (CD22+), and T cells expressing the T cell receptor gamma delta (TCR gamma delta) were found. Hardly any lymphoid cells with an NK phenotype (CD3-, CD56+) were present in the tumors studied. Large numbers of CD16+ cells were found, which could be identified as macrophages on the basis of their morphology, positive staining with a panel of monocyte/macrophage markers, and the results of double staining with CD11c.


CONCLUSIONS
We have demonstrated the presence of a large number of macrophages in the cellular infiltrates of several types of tumors. The largest numbers of CD16+ macrophages were found in renal cancer, melanoma, and colonic-carcinoma. These are the tumors that are most susceptible to immunotherapy with lymphokine activated killer cells, suggesting that these CD16+ macrophages may be involved in antitumor cytotoxicity. Furthermore, these findings suggest that new strategies of immunotherapy aimed at the use of macrophages present in many tumors could be developed.
van Ravenswaay Claasen
H H
HH
Department of Pathology, University of Leiden, The Netherlands.
Kluin
P M
PM
Fleuren
G J
GJ
D015703:Antigens, CD / Q000032:analysis; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007124:Immunoenzyme Techniques; D016130:Immunophenotyping; D007167:Immunotherapy; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology
D015703:Antigens, CD