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Title:
An immune-active tumor microenvironment favors clinical response to ipilimumab | Cancer Immunology, Immunotherapy
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Purpose Ipilimumab, a fully human monoclonal antibody specific to CTLA-4, has been shown to improve overall survival in metastatic melanoma patients. As a consequence of CTLA-4 blockade, ipilimumab treatment is associated with proliferation and activation of peripheral T cells. To better understand various tumor-associated components that may influence the clinical outcome of ipilimumab treatment, gene expression profiles of tumors from patients treated with ipilimumab were characterized. Experimental design Gene expression profiling was performed on tumor biopsies collected from 45 melanoma patients before and 3 weeks after the start of treatment in a phase II clinical trial. Results Analysis of pre-treatment tumors indicated that patients with high baseline expression levels of immune-related genes were more likely to respond favorably to ipilimumab. Furthermore, ipilimumab appeared to induce two major changes in tumors from patients who exhibited clinical activity: genes involved in immune response showed increased expression, whereas expression of genes for melanoma-specific antigens and genes involved in cell proliferation decreased. These changes were associated with the total lymphocyte infiltrate in tumors, and there was a suggestion of association with prolonged overall survival in these patients. Many IFN-γ-inducible genes and Th1-associated markers showed increased expression after ipilimumab treatment, suggesting an accumulation of this particular type of T cell at the tumor sites, which might play an important role in mediating the antitumor activity of ipilimumab. Conclusions These results support the proposed mechanism of action of ipilimumab, suggesting that cell-mediated immune responses play an important role in the antitumor activity of ipilimumab.
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google, scholar, pubmed, article, cas, cancer, melanoma, ipilimumab, patients, expression, cell, clinical, cells, gene, human, med, tumor, metastatic, immune, immunotherapy, survival, genes, national, immunol, wang, ctla, responses, proceedings, academy, sciences, united, states, america, privacy, cookies, content, data, chasalow, berman, tumors, profiling, activity, chen, robert, res, analysis, publish, research, search, microenvironment,
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month download article/chapter interferon-gamma-induced gene expression article cancer immunology gene expression profiling multiple cancer/testis antigens immune-mediated tumor destruction anti-ctla-4 therapy results tumor microenvironment biomarkers cd8+ t-cell recruitment gene expression profiles ifn-γ-inducible genes therapeutic antitumor efficacy cell line-tropic hiv-1 immunotherapy article bristol-myers squibb cancer immunotherapy human tyrosinase gene full article pdf privacy choices/manage cookies ceacam1 enhances invasion jackson & vafa shahabi breast cancer patients melanocyte-specific transcription ctla-4-mediated inhibition tumor immunotherapy immune-related genes ifn-gamma levels melanoma-specific antigens human cancer cells t-cell responses adaptive immune responses therapeutic potential allogeneic antibody screening total lymphocyte infiltrate national cancer institute trail-induced apoptosis tumor biopsies collected article ji immune response sox10 transcription factors cell alpha chemoattractant european economic area immunotherapy aims maria jure-kunkel gov/csr/1975_2008/ braf v600e mutation higher cd4+ icoshi lymphoattractant c-x e89–e94 yasumoto ortiz romero pl
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headline:An immune-active tumor microenvironment favors clinical response to ipilimumab
description:Ipilimumab, a fully human monoclonal antibody specific to CTLA-4, has been shown to improve overall survival in metastatic melanoma patients. As a consequence of CTLA-4 blockade, ipilimumab treatment is associated with proliferation and activation of peripheral T cells. To better understand various tumor-associated components that may influence the clinical outcome of ipilimumab treatment, gene expression profiles of tumors from patients treated with ipilimumab were characterized. Gene expression profiling was performed on tumor biopsies collected from 45 melanoma patients before and 3 weeks after the start of treatment in a phase II clinical trial. Analysis of pre-treatment tumors indicated that patients with high baseline expression levels of immune-related genes were more likely to respond favorably to ipilimumab. Furthermore, ipilimumab appeared to induce two major changes in tumors from patients who exhibited clinical activity: genes involved in immune response showed increased expression, whereas expression of genes for melanoma-specific antigens and genes involved in cell proliferation decreased. These changes were associated with the total lymphocyte infiltrate in tumors, and there was a suggestion of association with prolonged overall survival in these patients. Many IFN-γ-inducible genes and Th1-associated markers showed increased expression after ipilimumab treatment, suggesting an accumulation of this particular type of T cell at the tumor sites, which might play an important role in mediating the antitumor activity of ipilimumab. These results support the proposed mechanism of action of ipilimumab, suggesting that cell-mediated immune responses play an important role in the antitumor activity of ipilimumab.
datePublished:2011-12-07T00:00:00Z
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Metastatic melanoma
Cytotoxic T lymphocyte antigen-4
Gene expression profiling
Immunotherapy
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headline:An immune-active tumor microenvironment favors clinical response to ipilimumab
description:Ipilimumab, a fully human monoclonal antibody specific to CTLA-4, has been shown to improve overall survival in metastatic melanoma patients. As a consequence of CTLA-4 blockade, ipilimumab treatment is associated with proliferation and activation of peripheral T cells. To better understand various tumor-associated components that may influence the clinical outcome of ipilimumab treatment, gene expression profiles of tumors from patients treated with ipilimumab were characterized. Gene expression profiling was performed on tumor biopsies collected from 45 melanoma patients before and 3 weeks after the start of treatment in a phase II clinical trial. Analysis of pre-treatment tumors indicated that patients with high baseline expression levels of immune-related genes were more likely to respond favorably to ipilimumab. Furthermore, ipilimumab appeared to induce two major changes in tumors from patients who exhibited clinical activity: genes involved in immune response showed increased expression, whereas expression of genes for melanoma-specific antigens and genes involved in cell proliferation decreased. These changes were associated with the total lymphocyte infiltrate in tumors, and there was a suggestion of association with prolonged overall survival in these patients. Many IFN-γ-inducible genes and Th1-associated markers showed increased expression after ipilimumab treatment, suggesting an accumulation of this particular type of T cell at the tumor sites, which might play an important role in mediating the antitumor activity of ipilimumab. These results support the proposed mechanism of action of ipilimumab, suggesting that cell-mediated immune responses play an important role in the antitumor activity of ipilimumab.
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Metastatic melanoma
Cytotoxic T lymphocyte antigen-4
Gene expression profiling
Immunotherapy
Oncology
Immunology
Cancer Research
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