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A highly immunogenic tumor transfected with a murine transforming growth factor type beta 1 cDNA escapes immune
G Torre-Amione1, R D Beauchamp, H Koeppen
1Department of Pathology, University of Chicago, IL 60637.
Abstract:
A highly immunogenic C3H-derived UV-induced tumor was cotransfected with a murine transforming growth factor type beta 1 (TGF-beta 1) cDNA and a neomycin-resistance gene. Stable clones were isolated and used in vitro and in vivo to determine the effects of endogenously produced TGF-beta on cytolytic T-lymphocyte (CTL) responses. Tumor cells producing TGF-beta, though retaining expression for class I major histocompatibility complex molecules and the tumor-specific antigen, did not stimulate primary CTL responses in vitro and were not effective in vivo for directly stimulating primary CTL or in priming for CTL responses. Furthermore, TGF-beta-producing tumors grew progressively in transiently immunosuppressed mice without losing the tumor antigen; thus, TGF-beta produced by tumors may promote escape from immune surveillance.
Insights
Transforming growth factor beta 1 (TGF-beta 1) produced by tumors impairs T-lymphocyte responses, hindering immune surveillance and promoting tumor growth. This study reveals TGF-beta's role in immune evasion.
Area of Science:
- Immunology
- Cancer Biology
- Molecular Biology
Background:
- Tumor cells can evade immune detection through various mechanisms.
- Transforming growth factor beta 1 (TGF-beta 1) is a cytokine with known immunosuppressive properties.
Purpose of the Study:
- To investigate the impact of endogenously produced TGF-beta 1 on T-lymphocyte responses against a tumor.
- To determine if TGF-beta 1 production by tumor cells contributes to immune evasion and tumor progression.
Main Methods:
- C3H-derived UV-induced tumor cells were cotransfected with TGF-beta 1 cDNA and a neomycin-resistance gene.
- Stable clones producing TGF-beta 1 were generated and tested in vitro and in vivo.
- Cytolytic T-lymphocyte (CTL) responses were assessed in the presence of TGF-beta 1-producing tumor cells.
Main Results:
- Tumor cells engineered to produce TGF-beta 1 failed to stimulate primary CTL responses in vitro.
- These TGF-beta 1-producing tumor cells were ineffective in directly stimulating or priming CTL responses in vivo.
- Tumors producing TGF-beta 1 exhibited progressive growth in immunosuppressed mice without loss of tumor antigen expression.
Conclusions:
- Endogenously produced TGF-beta 1 by tumor cells significantly inhibits anti-tumor CTL responses.
- TGF-beta 1 production by tumors appears to be a critical mechanism for immune evasion, promoting tumor escape from immune surveillance.