Properties of recombinant interleukin 2-cultured tumor-infiltrating lymphocytes in human lung cancer.
It is thought that TIL can be activated in vitro by rIL-2 and acquire specific anti-tumor activity. In this study, we investigated this possibility, using lymphocytes isolated from primary lung cancer tissues. In a first series of experiments, TILs and autologous PBLs from 16 patients were cultured in rIL-2 from 7 to 14 days under identical conditions, and were compared for proliferation (16 cases), cytolytic activity (11 cases), gamma interferon (IFN-gamma) production (8 cases), and phenotypes (10 cases). TILs grew in response to rIL-2 as well as PBLs. However, the induced cytolytic activity of TIL was significantly lower than that of PBL against autologous tumor cells and 2 human tumor cell lines. IL-2-mediated IFN-gamma production by TILs was also significantly lower than that of PBLs. TILs were phenotypically characterized by their high CD4/CD8 ratio and lack of Leu11-positive cells. Further investigations with 7 other cases showed that exogenous addition of IFN-gamma to rIL-2 cultures of TILs enhanced cytolytic activity in 4 cases. Our results indicate that IL-2 alone is sufficient for TILs to proliferate but not to acquire new functions (cytotoxicity and production of IFN-gamma).
Yano
T
T
Department of Immunology, Kyushu University, Fukuoka, Japan.
Yasumoto
K
K
Togami
M
M
Ishida
T
T
Kimura
G
G
Sugimachi
K
K
Nomoto
K
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002469:Cell Separation; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D011994:Recombinant Proteins; D007371:Interferon-gamma