Interleukin-7 gene transfer in non-small-cell lung cancer decreases tumor proliferation, modifies cell surface molecule expression, and enhances antitumor reactivity.
Cytokine gene transfer to tumor cells can augment host antitumor responses and modify tumor phenotype. To evaluate the immunoregulatory and antitumor capacities of lung tumor-derived interleukin-7 (IL-7), we transduced non-small-cell lung cancer (NSCLC) cell lines with the IL-7/HyTK internal ribosomal entry site (IRES) retroviral vector and evaluated modifications in tumor phenotype and cocultured effector activities. In vitro proliferation of IL-7-transduced tumor cells was significantly less than control vector-transduced and parental tumor cells. The decreased proliferation rates of IL-7-transduced cells could be reproduced by adding high concentrations of recombinant IL-7 to the parental cells. Anti-IL-7 monoclonal antibody significantly increased the proliferation of the IL-7-transduced cells (P < .05). Parental NSCLC cells were found to express the IL-7 receptor, and IL-7 gene transduction did not alter expression of the IL-7 receptor. IL-7 transduction significantly altered tumor cell expression of intracellular adhesion molecule 1, major histocompatibility complex 1, lymphocyte function-related antigen 3, very late activation antigen beta 1, and p185neu. Peripheral blood lymphocytes cocultured with either IL-7-transduced tumor cells or tumor supernatants had enhanced cytolytic and proliferative capacities compared with coculture with control vector-transduced or parental cells. Our findings indicate that IL-7 gene transfer in NSCLC significantly augments cocultured effector activities in vitro, inhibits tumor cell proliferation, and modifies tumor cell surface phenotype. These findings suggest that IL-7 gene therapy may be effective in modifying host antitumor responses in NSCLC.
Pulmonary Immunology Laboratory, UCLA School of Medicine, USA.
S
S
Sharma
J
J
Wang
M
M
Huang
R W
RW
Paul
P
P
Lee
W H
WH
McBride
J S
JS
Economou
M D
MD
Roth
S M
SM
Kiertscher
S M
SM
Dubinett
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000954:Antigens, Surface / Q000378:metabolism; D002455:Cell Division / Q000235:genetics*; D018920:Coculture Techniques; D003470:Culture Media / Q000494:pharmacology; D015774:Ganciclovir / Q000494:pharmacology / Q000633:toxicity; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015851:Interleukin-7 / Q000235:genetics* / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism*; D008979:Moloney murine leukemia virus / Q000235:genetics; D016133:Polymerase Chain Reaction; D012190:Retroviridae / Q000235:genetics; D014161:Transduction, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D003470:Culture Media; D015851:Interleukin-7; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D015774:Ganciclovir