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.
Keller
H
H
Department of General Surgery, University of Freiburg, Germany.
Wimmenauer
S
S
Rahner
S
S
Von Kleist
S
S
Farthmann
E H
EH
D000328:Adult; D000368:Aged; D002455:Cell Division; D015179:Colorectal Neoplasms / Q000276:immunology*; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D016131:Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D016246:Lymphocytes, Tumor-Infiltrating / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011994:Recombinant Proteins / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology
D007376:Interleukin-2; D011994:Recombinant Proteins; D015847:Interleukin-4