A nonimmunogenic sarcoma transduced with the cDNA for interferon gamma elicits CD8+ T cells against the wild-type tumor: correlation with antigen presentation capability.
A nonimmunogenic sarcoma transduced with the cDNA for interferon gamma elicits CD8+ T cells against the wild-type tumor: correlation with antigen presentation capability.
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DOI：
10.1084/jem.175.6.1423
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发表时间：
1992-06-01
影响因子：
15.3
通讯作者：
ROSENBERG, SA
中科院分区：
文献类型：
--
作者：
RESTIFO, NP;SPIESS, PJ;KARP, SE;MULE, JJ;ROSENBERG, SA
To be recognized by CD8+ T lymphocytes, target cells must process and present peptide antigens in the context of major histocompatibility complex (MHC) class I molecules. The nonimmunogenic, low class I- expressing, methylcholanthrene (MCA)-induced murine sarcoma cell line, MCA 101, is a poor presenter of endogenously generated viral antigens to specific CD8+ T lymphocytes and cannot be used to generate tumor infiltrating lymphocytes (TIL). Since interferon gamma (IFN-gamma) has been shown to upregulate three sets of molecules important for antigen processing and presentation, we retrovirally transduced wild-type MCA 101 (101.WT) tumor with the mIFN-gamma cDNA to create the 101.NAT cell line. Unlike 101.WT, some clones of retrovirally transduced 101.NAT tumor expressed high levels of class I, and could be used to generate CD8+ TIL. More importantly, these TIL were therapeutic in vivo against established pulmonary metastases from the wild-type tumor. Although not uniformly cytotoxic amongst several separate cultures, these TIL did specifically release cytokines (IFN-gamma and tumor necrosis factor- alpha) in response to 101.WT targets. 101.WT's antigen presentation deficit was also reversed by gene modification with mIFN-gamma cDNA. 101.NAT had a greatly improved capacity to present viral antigens to CD8+ cytotoxic T lymphocytes. These findings show that a nonimmunogenic tumor, incapable of generating a CD8+ T cell immune response, could be gene-modified to generate a therapeutically useful immune response against the wild-type tumor. This strategy may be useful in developing treatments for tumor histologies not thought to be susceptible to T cell-based immunotherapy.
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DOI：
10.1084/jem.174.2.425
发表时间：
1991-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Falk K;Rötzschke O;Deres K;Metzger J;Jung G;Rammensee HG
通讯作者：
Rammensee HG
影响因子：
64.8
作者：
DEVERSON, EV;GOW, IR;HOWARD, JC
通讯作者：
HOWARD, JC
影响因子：
64.5
作者：
FEARON, ER;PARDOLL, DM;FROST, P
通讯作者：
FROST, P
DOI：
10.1084/jem.168.4.1419
发表时间：
1988-10-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Itoh K;Platsoucas CD;Balch CM
通讯作者：
Balch CM
DOI：
10.1084/jem.173.3.647
发表时间：
1991-03-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Barth RJ Jr;Mulé JJ;Spiess PJ;Rosenberg SA
通讯作者：
Rosenberg SA