Immune Signatures Predict Prognosis in Localized Cancer

David S HsuDuke Institute for Genome Sciences and Policy, Division of Medical Oncology, Department of Internal Medicine, Duke University Medical Center, Durham, North Carolina, USA, Division of Medical Oncology, Department of Internal Medicine, University of North Carolina, Chapel Hill, North Carolina, USA, Duke Comprehensive Cancer Center, Duke University Medical Center, Durham, North Carolina, USA, Division of Medical Oncology, Urology and Immunology, Johns Hopkins SKCCC, Baltimore, Maryland, USA, Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA.

Mickey K KimDuke Institute for Genome Sciences and Policy, Division of Medical Oncology, Department of Internal Medicine, Duke University Medical Center, Durham, North Carolina, USA, Division of Medical Oncology, Department of Internal Medicine, University of North Carolina, Chapel Hill, North Carolina, USA, Duke Comprehensive Cancer Center, Duke University Medical Center, Durham, North Carolina, USA, Division of Medical Oncology, Urology and Immunology, Johns Hopkins SKCCC, Baltimore, Maryland, USA, Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA.

Bala S. BalakumaranDuke Institute for Genome Sciences and Policy, Division of Medical Oncology, Department of Internal Medicine, Duke University Medical Center, Durham, North Carolina, USA, Division of Medical Oncology, Department of Internal Medicine, University of North Carolina, Chapel Hill, North Carolina, USA, Duke Comprehensive Cancer Center, Duke University Medical Center, Durham, North Carolina, USA, Division of Medical Oncology, Urology and Immunology, Johns Hopkins SKCCC, Baltimore, Maryland, USA, Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA.

Chaitanya R AcharyaDuke Institute for Genome Sciences and Policy, Division of Medical Oncology, Department of Internal Medicine, Duke University Medical Center, Durham, North Carolina, USA, Division of Medical Oncology, Department of Internal Medicine, University of North Carolina, Chapel Hill, North Carolina, USA, Duke Comprehensive Cancer Center, Duke University Medical Center, Durham, North Carolina, USA, Division of Medical Oncology, Urology and Immunology, Johns Hopkins SKCCC, Baltimore, Maryland, USA, Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA.

Carey K AndersDuke Institute for Genome Sciences and Policy, Division of Medical Oncology, Department of Internal Medicine, Duke University Medical Center, Durham, North Carolina, USA, Division of Medical Oncology, Department of Internal Medicine, University of North Carolina, Chapel Hill, North Carolina, USA, Duke Comprehensive Cancer Center, Duke University Medical Center, Durham, North Carolina, USA, Division of Medical Oncology, Urology and Immunology, Johns Hopkins SKCCC, Baltimore, Maryland, USA, Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA.

Tim ClayDuke Institute for Genome Sciences and Policy, Division of Medical Oncology, Department of Internal Medicine, Duke University Medical Center, Durham, North Carolina, USA, Division of Medical Oncology, Department of Internal Medicine, University of North Carolina, Chapel Hill, North Carolina, USA, Duke Comprehensive Cancer Center, Duke University Medical Center, Durham, North Carolina, USA, Division of Medical Oncology, Urology and Immunology, Johns Hopkins SKCCC, Baltimore, Maryland, USA, Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA.

H. Kim LyerlyDuke Institute for Genome Sciences and Policy, Division of Medical Oncology, Department of Internal Medicine, Duke University Medical Center, Durham, North Carolina, USA, Division of Medical Oncology, Department of Internal Medicine, University of North Carolina, Chapel Hill, North Carolina, USA, Duke Comprehensive Cancer Center, Duke University Medical Center, Durham, North Carolina, USA, Division of Medical Oncology, Urology and Immunology, Johns Hopkins SKCCC, Baltimore, Maryland, USA, Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA.

Charles G. DrakeDuke Institute for Genome Sciences and Policy, Division of Medical Oncology, Department of Internal Medicine, Duke University Medical Center, Durham, North Carolina, USA, Division of Medical Oncology, Department of Internal Medicine, University of North Carolina, Chapel Hill, North Carolina, USA, Duke Comprehensive Cancer Center, Duke University Medical Center, Durham, North Carolina, USA, Division of Medical Oncology, Urology and Immunology, Johns Hopkins SKCCC, Baltimore, Maryland, USA, Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA.

Michael A. MorseDuke Institute for Genome Sciences and Policy, Division of Medical Oncology, Department of Internal Medicine, Duke University Medical Center, Durham, North Carolina, USA, Division of Medical Oncology, Department of Internal Medicine, University of North Carolina, Chapel Hill, North Carolina, USA, Duke Comprehensive Cancer Center, Duke University Medical Center, Durham, North Carolina, USA, Division of Medical Oncology, Urology and Immunology, Johns Hopkins SKCCC, Baltimore, Maryland, USA, Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA.

Phillip G. FebboDuke Institute for Genome Sciences and Policy, Division of Medical Oncology, Department of Internal Medicine, Duke University Medical Center, Durham, North Carolina, USA, Division of Medical Oncology, Department of Internal Medicine, University of North Carolina, Chapel Hill, North Carolina, USA, Duke Comprehensive Cancer Center, Duke University Medical Center, Durham, North Carolina, USA, Division of Medical Oncology, Urology and Immunology, Johns Hopkins SKCCC, Baltimore, Maryland, USA, Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA.

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ABSTRACT

The host immune response can impact cancer growth, prognosis, and response to therapy. In colorectal cancer, the presence of cells involved with T-cell-mediated adaptive immunity predicts survival better than the current staging method. We used the expression of genes recently associated with host immune responses (T_H1-mediated adaptive immunity, inflammation, and immune suppression) to perform hierarchical clustering of multiple large cohorts of cancer specimens to determine if immune-related gene expression resulted in clinical significant groupings of tumors. Microarray data from prostate cancer (n = 79), breast cancer (n = 132), lung cancer (n = 84), glioblastoma multiforme (n = 120), and lymphoma (n = 127) were analyzed. Among adenocarcinomas, the T_H1-mediated adaptive immunity genes were consistently associated with better prognosis, while genes associated with inflammation and immune suppression were variably associated with outcome. Specifically, increased expression of the T_H1-mediated adaptive immunity genes was associated with good prognosis in breast cancer patients under 45 years of age (p = .04, hazard ratio [HR] = 0.42) and in prostate cancer patients (p = .03, HR = 0.36) but not in lung cancer patients (p = 0.45, HR = 1.37). In lymphoma, patients with increased expression of inflammation and immune suppression genes had better prognosis than those expressing the T_H1-mediated adaptive immunity genes (p = .01, HR = 0.43) and in glioblastoma multiforme, the expression of inflammation genes conferred improved prognosis than those expressing immune suppression genes (p = 0.05, HR = 0.62). In aggregate, the gene expression signatures implicating specific components of the immune response hold prognostic import across solid tumors.

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Immune Signatures Predict Prognosis in Localized Cancer

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