Lack of correlation between defective cell-mediated immunity and levels of secreted or circulating cytokines in a study of 90 cancer patients

In this study we examined the levels of IL-1a, IL-1β, IL-2, IL-6, TNF-α and sIL-2R in the sera and culture supernatants of PHA-stimulated lymphocytes from a series of 90 cancer patients. The expression of the IL-2R p55 chain (α subunit) on PHA-stimulated lymphocytes was also evaluated together with the blastogenic response of peripheral blood mononuclear cells (PBMC) to PHA, PHA plus rIL-2 and rIL-2 alone. Ninety cancer patients (70 men and 20 women; mean age 57.8 years, range 27-80) with advanced solid malignancies at different sites were studied. The lymphocyte blastogenic response to PHA was significantly lower in cancer patients than in normal individuals. The proliferative response to rIL-2 alone was also significantly depressed in cancer patients. The frequency of CD25+ PHA-stimulated lymphocytes from cancer patients was not significantly different from that of the control group. The serum values for IL-1α, IL-1β, IL-6 and sIL-2R were significantly higher in cancer patients than in controls, while the serum level of IL-2 was within the normal range. The levels of sIL-2R released in the supernatant of PHA-stimulated PBMC of cancer patients were significantly lower than those of the control group. However, the levels of IL-1α, IL-1β, IL-2, IL-6 and TNF-α in the supernatants of PHA-stimulated PBMC of cancer patients were in the same range as those of the control group. These results suggest that the observed immuno-deficiency in cancer patients cannot be explained on the basis of a defective production of key immunoregulatory cytokines since the lymphocytes from cancer patients produced physiological amounts of cytokines. We suggest that the observed defective cell-mediated immunity may be due to a defect in transmembrane signalling by the cytokines.