IMMUNOMODULATORY EFFECTS OF INTERLEUKIN-12 ON HUMAN TUMOR-INFILTRATING LYMPHOCYTES

Interleukin (IL)-12 is a recently described cytokine with multiple imm unoregulatory effects on various lymphoid populations. including perip heral blood lymphocytes (PBL), natural killer (NK) cells, and T-cell s ubsets. We examined the effects of recombinant IL-12 on the immune fun ction of human tumor infiltrating lymphocytes (TIL) from several diffe rent tumor types. At an optimal concentration of 50 IU/ml, IL-12 acted as a co-stimulant for TIL recently activated with anti-CD3 antibodies , giving stimulation indices between 2.6 and 9.9. This co-stimulatory effect was independent of IL-2 and was not inhibited by neutralizing a ntibody to human IL-2. When IL-2 and IL-12 were used synchronously as co-mitogenic stimuli in culture with activated TIL, the effect on prol iferation was additive. This additive effect held true over a range of suboptimal concentrations of IL-2 and in different TIL populations. I L-12 did not enhance non-major histocompatability complex (MHC)-restri cted cytotoxicity in the TIL populations tested. TIL cultured with IL- 12 killed more autologous tumor targets than TIL maintained in media a lone at identical effector/target (E/T) ratios. This effect on cytotox icity was not as great as that seen in TIL maintained in low-dose IL-2 . Co-culture with IL-12 did not change the phenotype of TIL used in th ese assays. The importance of these findings and possible uses in immu notherapy are discussed.