INTERLEUKIN-2-ACTIVATED KILLER-CELL ACTIVITY IN COLORECTAL TUMOR PATIENTS - EVALUATION OF IN-VITRO EFFECTS BY PROTHYMOSIN ALPHA-1

The effects of prothymosin alpha 1 (Pro alpha 1) in combination with i nterleukin-2 (IL-2) on peripheral blood lymphocytes from 50 colorectal tumor patients at different stages were studied with respect to immun ocytotoxicity, adhesion to cultured SW620 colon carcinoma cells, secre tion of cytokines and expression of adhesion and surface marker molecu les. On average, the patients showed lower natural killer (NK) cell ac tivity than healthy donors, which was associated with a lower adhesion capacity to the tumor target cells. The NK cell activity of the patie nts was inversely related to the tumor stage. The generation of lympho kine(IL-2)-activated killer (LAK) cell activity was found to be compar able on lymphocytes from healthy individuals and patients and was not correlated to tumor stage. Pro alpha 1 stimulated patients' LAK cell a ctivity only, primarily at the early stage (Dukes A/B). The Pro alpha 1 effect was associated with an increased adhesion of lymphocytes to t umor target cells and an increased secretion of the deficient IL-2-ind uced IFN gamma secretion. No significant effects on the low level of T NF alpha secretion was noted. By flow cytometry, Pro alpha 1 in combin ation with IL-2 augmented the expression of the NK cell markers CD56, CD16/56, the subset CD3/16/56 and CD25 on lymphocytes of the patients. In contrast, Pro al was equally effective by increasing the expressio n of CD18 and CD11a on lymphocytes from the patients and from normal c ontrols. In conclusion, Pro alpha 1, in combination with IL-2, can par tially normalize lymphocyte deficiencies of colon cancer patients in v itro. This potential might provide an experimental basis for applying Pro alpha 1 or related thymic peptides in selected immunotherapies aga inst colorectal tumors.