Characterization of tumor-necrosis-factor-gene-transduced tumor-infiltrating lymphocytes from ascitic fluid of cancer patients: analysis of cytolytic activity, growth rate, adhesion molecule expression and cytokine production.
We characterized tumor-infiltrating lymphocytes (TIL) from ascites of patients with ovarian or pancreatic cancer in which the human tumor necrosis factor (TNF) gene was successfully transduced with retrovirus vector. The TNF-gene-transduced TIL (TNF-TIL) from these patients showed a higher level of TNF production and higher cytotoxic activity against K562 and Daudi cells than did neomycin-phosphotransferase-gene-transduced TIL (neo-TIL). Of these TIL preparations, only that from pancreatic cancer was further characterized since it was collected in a relatively large amount. In spite of the fact that the autologous tumor cells showed resistance to soluble TNF, the TNF-TIL clearly demonstrated enhanced cytotoxicity against them as compared with neo-TIL. The enhanced cytotoxicity was ascribed to autocrine effects of secreted TNF on TIL, which included augmentation of adhesion molecule (CD2 and CD11a) and interleukin-2 receptor expression, and elevation of production of interferon gamma, lymphotoxin and granulocyte/macrophage-colony-stimulating factor and its paracrine effect on target cells to facilitate them to be more susceptible to TIL.
Itoh
Y
Y
Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, Japan.
Koshita
Y
Y
Takahashi
M
M
Watanabe
N
N
Kohgo
Y
Y
Niitsu
Y
Y
D001201:Ascites; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002455:Cell Division; D016207:Cytokines / Q000096:biosynthesis*; D003602:Cytotoxicity, Immunologic; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D010051:Ovarian Neoplasms / Q000628:therapy; D010190:Pancreatic Neoplasms / Q000628:therapy; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D014161:Transduction, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D015815:Cell Adhesion Molecules; D016207:Cytokines; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha