Phenotypical and functional differences of tumor-infiltrating lymphocytes from human colorectal cancers induced by costimulation with rIL-2 and rIL-4 in vitro.

The influence of recombinant human interleukin-4 (rIL-4) on the proliferation and cytotoxic activity of tumor-infiltrating lymphocytes (TIL) from human colorectal cancers was investigated TIL and peripheral blood lymphocytes (PBL) were cultured for 3-5 weeks. Under simultaneous stimulation with rIL-2 and rIL-4 the proliferation of TIL was less pronounced compared to stimulation with rIL-2 alone. In rIL-2 expanded TIL an outgrowth of CD56+ cells was observed. Concordantly, the expression of CD3+ cells was low. The number of CD56+ cells could be reduced significantly in TIL and PBL by stimulation with rIL-2 and rIL-4 simultaneously 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 compared 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 against autologous tumor targets in comparison to the rIL-2 expanded lymphocytes. In contrast, the cytotoxic activity of rIL-2/rIL-4 cultured TIL against allogeneic tumor cells was higher than in rIL-2 stimulated TIL.