Tube leukocyte (monocyte) adherence inhibition assay for the detection of anti-tumour immunity. III. "Blockade" of monocyte reactivity by excess free antigen and immune complexes in advanced cancer patients.
Leukocytes from patients with limited cancer display LAI reactivity whereas leukocytes from patients with metastatic cancer frequently demonstrate no reactivity in the tube LAI assay. The leukocytes (monocytes) of reactive patients react with tumour antigen through specific cytophilic anti-tumour IgG antibody bound to the monocyte's Fc cell surface receptors. The non-reactive monocytes from patients with advanced cancer lacked the ability to bind free cytophilic anti-tumour antibody. Moreover, the serum of the non-reactive patient contained no free cytophilic anti-tumour antibody capable of "arming" normal leukocytes. The serum of patients with large tumour burdens contained free tumour antigenic determinants capable of absorbing free cytophilic anti-tumour antibody from the serum of reactive patients or when preincubated with reactive leukocytes abrogating their LAI responsiveness immunologically specifically. Blocking was immunologically specific; therefore, the specificity must reside in the tumour antigenic determinant since immune complexes are bound nonspecifically. The tumour antigen coat was removed by gentle trypsinization of the monocyte's surface. This restored the monocyte's capacity to react with the sensitizing tumour antigen and to bind free cytophilic antibody from the microenvironment. Nonreactivity in the tube LAI assay of patients with metastatic cancer was not the result of a numerical deficit of circulating monocytes but was mediated by an excess of tumour antigen in the microenvironment of the sensitized monocyte.
D000230:Adenocarcinoma / Q000276:immunology; D000912:Antibodies, Neoplasm; D000936:Antigen-Antibody Complex; D000937:Antigen-Antibody Reactions; D000951:Antigens, Neoplasm; D001667:Binding, Competitive; D001943:Breast Neoplasms / Q000276:immunology*; D002448:Cell Adhesion; D002464:Cell Migration Inhibition; D003429:Cross Reactions; D000939:Epitopes; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008545:Melanoma / Q000276:immunology; D009000:Monocytes / Q000276:immunology*; D009362:Neoplasm Metastasis; D014357:Trypsin / Q000494:pharmacology
D000912:Antibodies, Neoplasm; D000936:Antigen-Antibody Complex; D000951:Antigens, Neoplasm; D000939:Epitopes; D014357:Trypsin