Infiltration of interleukin-2-inducible killer cells in ascitic fluid and pleural effusions of advanced cancer patients.
Using ascitic fluid or pleural effusion obtained from 13 ovarian or metastatic breast cancer patients, we separated tumor cells from effusion-associated lymphocytes (EAL) with Percoll density centrifugation. Lymphocytes were incubated with recombinant interleukin 2 (IL-2) for 3-4 days and then assessed for tumoricidal activity in a 51chromium-release assay. The IL-2-activated EAL were found to lyse autologous fresh tumor cells, as well as allogeneic fresh tumor cells and FMEX tumor cells, a melanoma cell line which is resistant to natural killer cell activity but is sensitive to lysis by lymphokine-activated killer cells. There was little or no tumoricidal activity seen in freshly isolated EAL or in EAL which were cultured in medium without IL-2. Phenotypically, the IL-2-activated EAL were largely CD3-, although some cytolytic activity was found in CD3+ populations. Also, most activity was found in cells positive for CD2 (OKT11) and CD16 (Leu 11b), and negative for the monocyte marker Leu M3. These results indicate that the activated cell types found in EAL were predominantly natural killer/lymphokine-activated killer-like with a small contribution from T-cells. Finally, EAL were readily activated by IL-2 in medium containing autologous effusion fluid, indicating that in situ activation of tumoricidal activity by IL-2 can occur in the face of potentially inhibitory substances or cells that may exist in the effusions. Direct introduction of IL-2 may therefore be a potential therapeutic modality of effusion-forming cancers.
Blanchard
D K
DK
Department of Medical Microbiology and Immunology, University of South Florida College of Medicine, Tampa 33612.
Kavanagh
J J
JJ
Sinkovics
J G
JG
Cavanagh
D
D
Hewitt
S M
SM
Djeu
J Y
JY
D000328:Adult; D000368:Aged; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001202:Ascitic Fluid / Q000276:immunology*; D017252:CD3 Complex; D002458:Cell Fractionation; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology*; D010641:Phenotype; D010996:Pleural Effusion / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D014407:Tumor Cells, Cultured
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell