Comparison by leukocyte adherence inhibition of human immune response to cancer-associated immunogens, Thomsen-Friedenreich (T) and Tn, myelin basic protein, and organ-specific cancer neoantigens.
Peripheral blood leukocytes from cancer patients exhibit nonadherence to glass as an index of antigen recognition when incubated individually with four distinct, soluble tumor-related substances. Crude cancer extracts, purified antigens, T and Tn, myelin basic protein (MBP), and organ-specific cancer neoantigens (OSN), all elicited narrow dose-dependent leukocyte adherence inhibition (LAI) response curves. The present study focused on the reasons for the narrow antigen dose-LAI response relationship. Between 9 and 20 pmol of antigens elicited the maximum number of nonadherent leukocytes; cleavage products of T antigen and the nonapeptide (T18) of MBP required about a 10-fold increase in molar concentration for the same LAI response. When crude cancer extracts were combined with pure antigen or the pure antigens were combined at concentrations shown to give maximum LAI responses, the positive LAI responses were negated. The chemoattractant LTB4 at 10(-11) M triggered maximum LAI. But when MBP was added with the LTB4 at progressively increasing concentrations, there was dose-dependent negation of LAI. The magnitude of LAI depended on the total amount of mediator released rather than the rate of release. When leukocytes from cancer patients were incubated with optimum to high concentrations of MBP, the supernatants contained a mediator that gave similar bell-shaped dose-LAI responses on control leukocytes indicating that leukocytes from cancer patients react to a much broader range of antigen concentration than indicated by the LAI assay alone. High antigen dose negated LAI because of excess mediator production. Antigen-generated mediators had a biphasic effect inducing nonadherence and then adherence of leukocytes.
Thomson
D M
DM
Division of Clinical Immunology and Allergy, Montreal General Hospital, Quebec, Canada.
Springer
G F
GF
Desai
P R
PR
Scanzano
R
R
Gubersky
M
M
Shenouda
G
G
D000951:Antigens, Neoplasm / Q000276:immunology*; D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007158:Immunologic Techniques; D007957:Leukocyte Adherence Inhibition Test; D004676:Myelin Basic Protein / Q000276:immunology*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000502:physiology; D009928:Organ Specificity
D000951:Antigens, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor; D004676:Myelin Basic Protein; D009363:Neoplasm Proteins; C040286:Tn antigen; C042035:humoral leukocyte adherence inhibition factor, human; C050269:organ-specific neoantigen