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In some serums of patients with transitional cell carcinoma (TCC), a factor is present which induces lymphocytes from most donors with or without TCC to become cytotoxic against TCC-derived target cells. The induced cytotoxicity was directed against target cells derived from TCC's of the renal pelvis, ureter, and urinary bladder, but not against cells derived from normal kidney, bladder, testis, or skin or from renal cell carcinoma. Cytotoxicity occurred without complement but did not occur without effector cells.

Serum from a patient with transitional-cell carcinoma of the urinary tract, which induced lymphocyte-mediated cytotoxicity against the carcinoma, was studied to determine the active factor and characterize its mode of action. The active serum factor was an IgG immunoglobulin that induced cytotoxicity only in the presence of effector cells (lymphocytes) and did not require the presence of complement. Contact between the IgG and a tumor-associated antigen appeared to be required before cytotoxicity could be induced in the lymphocyte. The IgG induced lymphocytes from donors with and without transitional-cell carcinoma to become cytotoxic against cells derived from transitional-cell carcinoma of the renal pelvis, ureter, and bladder but not against normal adult or embryonic cells or against renal-cell-carcinoma cells. These characteristics indicate that the active serum factor is a lymphocyte-dependent antibody that is directed against an antigen associated with transitional-cell carcinoma. (N Engl J...

The interaction of antibodies and lymphocytes in their immune reaction against human transitional cell carcinomas was studied using the in vitro microcytotoxicity assay. A non-complement dependent, IgG antibody was detected in the serum of occasional transitional cell carcinoma patients, which induced cytotoxicity against transitional cell carcinoma target cells by lymphocytes from donors with and without transitional cell carcinoma. The observation that lymphocytes from transitional cell carcinoma donors were more sensitive to activation by this anti-transitional cell carcinoma, lymphocyte dependent antibody is compatible with the hypothesis that the surface of lymphocytes from some transitional cell carcinoma donors is coated in vivo with an anti-transitional cell carcinoma lymphocyte dependent antibody and that this antibody may be a significant factor in immunity to transitional cell carcinomas of the urinary tract.

Preliminary studies indicate that cancers of the genitourinary system contain unique tissue-specific tumor associated antigens, and that some patients develop an immune response to these antigens. Additional study will be required before the many nuances of the immunobiology of these tumors are better understood because research in this area is, in fact, just beginning. However, the methodology of tumor immunology is becoming more sophisticated and basic investigation in this area is receiving increased financial support. The practical goals of these research efforts are to develop new immunologic techniques for early detection and treatment. Although immunodiagnosis now appears to be possible for some tumors, further intensive study will be necessary before a rational approach to immunotherapy can be developed for urologic tumors.