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Depression of the Generation of Cell-mediated Cytotoxicity by Macrophage-like Suppressor Cells in Bladder Carcinoma Patients¹

Immunobiology Group, Department of Microbiology and Immunology [C. A. S., F. D., J. L. F.], and Division of Urology, Department of Surgery [C. V., S. B.], UCLA School of Medicine, Los Angeles, California 90024

Depressed T-lymphocyte function as assessed by delayed-type hypersensitivity reactions and in vitro proliferative response to mitogens is a characteristic finding in many types of solid tumors, including bladder carcinoma. Peripheral blood leukocytes from 16 patients with transitional cell carcinoma of the bladder were compared with age-matched, control subjects. Both the unfractionated leukocytes containing 10 to 30% monocytes and the lymphocyte-enriched preparations, obtained by monocyte depletion with iron filing ingestion, were analyzed. Mixed leukocyte culture-induced cytotoxicity was depressed in the patient group; the amount of depression was directly correlated to the extent of the disease. In patients who underwent surgical removal of tumor, the mixed leukocyte culture-induced cytotoxicity appeared normal. This mixed leukocyte culture-generated cytotoxic response was a more sensitive indicator of tumor effect than was the induced proliferative response. Removal of phagocytic or adherent monocytes from the responding cell population caused a significant increase in the generated cytotoxicity, especially in those patients with invasive disease. These suppressive effects could be partially reconstituted by quantitative addition of the separated monocytes back to the responding lymphocyte culture. The depressed lymphocyte-mediated cytotoxicity present in these bladder cancer patients was due, in a major part, to a circulating macrophage-like cell with active suppressor function.

¹ Supported in part by NIH Grants CA-16880, CA-12800, and AI-07126 and by a grant from the Concern Foundation, Inc. Part of this work was presented at the meeting for the American Association for Cancer Research, Inc., in San Diego, Calif., May 1980 (32).

² To whom requests for reprints should be addressed.

Received 3/ 9/81. Accepted 7/29/81.