Multiple concurrent immunoregulatory defects in cancer patients with depressed PHA-induced lymphocyte DNA synthesis

Abstract

Peripheral blood mononuclear leukocytes (PBL) from 12 of 30 patients with untreated disseminated solid tumors exhibited lymphoproliferative responses to the T-cell mitogen, phytohemagglutinin (PHA), which fell greater than 2 standard deviations (SD) below those of age-matched normal subjects. The possible contribution of immunoregulatory suppressor cell activity to impaired responsiveness was assessed by measuring, at a single assessment point for each patient, the percentages and absolute numbers of the T-cell subsets T G and T M, concanavalin A (Con A)-inducible suppressor cells, and the effects of 24-hr preculture and glass-adherent cell depletion on resultant PHA responses. The values obtained for each of these parameters in individual patients was considered to be abnormal if the patient value fell greater than 2 SD above or below the corresponding mean value exhibited by a group of age-matched normal subjects. All patients studied exhibited at least one abnormal immunoregulatory mechanism, while 9 of 12 patients had multiple immunoregulatory defects. Six patients exhibited depressed Con A-inducible suppression in confunction with increased 24-hr preculture-sensitive and/or glassadherent cell-mediated suppression, one of these having, in addition, aberrant T G/T M profiles. Two patients had increased levels of Con A-inducible suppression in association with increased glass-adherent suppressor cell activity, one of these having decreased percentages of T M cells and the other having increased percentages of T G cells. The final patient with multiple immunoregulatory defects had increased percentages of T G cells and increased levels of 24-hr preculture-sensitive and glass-adherent cell-mediated suppressor activity. We conclude that multiple immunoregulatory defects may coexist and contribute to immunodeficiency in cancer patients.