PHENOTYPICAL AND FUNCTIONAL DIFFERENCES OF TUMOR-INFILTRATING LYMPHOCYTES FROM HUMAN COLORECTAL CANCERS INDUCED BY COSTIMULATION WITH RIL-2AND R-IL-4 IN-VITRO

The influence of recombinant human interleukin-4 (rIL-4) on the prolif eration and cytotoxic activity of tumor-infiltrating lymphocytes (TIL) from human colorectal cancers was investigated. TIL and peripheral bl ood lymphocytes (PBL) were cultured for 3-5 weeks. Under simultaneous stimulation with rIL-2 and rIL-4 the proliferation of TIL was less pro nounced compared to stimulation with rIL-2 alone. In rIL-2 expanded TI L an outgrowth of CD56+ cells was observed. Concordantly, the expressi on of CD3+ cells was low. The number of CD56+ cells could be reduced s ignificantly in TIL and PBL by stimulation with rIL-2 and rIL-4 simult aneously, while the number of CD3+ cells increased. In TIL and PBL co- stimulation with rIL2 and rIL-4 resulted in higher CD4/CD8 ratios as c ompared to expansion with rIL-2 alone. In a 72 hour cytotoxicity assay the rIL-2/rIL-4 expanded TIL and PBL showed a lower lytic activity ag ainst autologous tumor targets in comparison to the rIL2 expanded lymp hocytes. In contrast, the cytotoxic activity of rIL-2/rIL-4 cultured T IL against allogeneic tumor cells was higher than in rIL-2 stimulated TIL.