LOCAL RELEASE OF IL-10 BY TRANSFECTED MOUSE MAMMARY ADENOCARCINOMA CELLS DOES NOT SUPPRESS BUT ENHANCES ANTITUMOR REACTION AND ELICITS A STRONG CYTOTOXIC LYMPHOCYTE AND ANTIBODY-DEPENDENT IMMUNE MEMORY

The cDNA coding for mouse IL-10 (mIL-10) was transduced into the paren tal cells of a spontaneous adenocarcinoma of BALB/c mice (TSA-pc), and clones secreting small, medium, and large quantities of IL-10 were se lected. In vivo, both low and high producer clones do not display an e nhanced ability to grow in H-2 and non-H-2 incompatible mice. Instead, the intensity of their rejection increases in function of the amount of mIL-10 released. After an initial growth period in syngeneic mice, high producer clones undergo complete rejection due to the combined ac tion of CD8(+) lymphocytes, NK cells, and neutrophils. After this reje ction, mice are immune to a subsequent challenge with TSA-pc. This mem ory rests on a strong lytic activity of CD8(+) CTL and granulocytes. F ollowing the rejection, mice also develop anti-TSA Ab that guide the g ranulocytes in TSA-pc memory reaction. A direct comparison shows that although TSA clones engineered to release IL-2 activate CTL and no ant i-TSA Ab, those engineered to release IL-4 activate a strong Ab respon se but not CTL. The kind of cytokine released by the tumors appears to determine the type of response. However, IL-10 high producer cells do not deviate the immune memory, neither toward a Th1 nor a Th2. Both t he CTL activity and the Ab responses induced by IL-10 high producer ce lls are the strongest so far observed in the TSA system.