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The landscape of T cell infiltration in human cancer and its association with antigen presenting gene expression

View ORCID ProfileYasin Şenbabaoğlu, View ORCID ProfileAndrew G. Winer, View ORCID ProfileRon S. Gejman, View ORCID ProfileMing Liu, View ORCID ProfileAugustin Luna, View ORCID ProfileIrina Ostrovnaya, View ORCID ProfileNils Weinhold, View ORCID ProfileWilliam Lee, View ORCID ProfileSamuel D. Kaffenberger, View ORCID ProfileYing Bei Chen, View ORCID ProfileMartin H. Voss, View ORCID ProfileJonathan A. Coleman, View ORCID ProfilePaul Russo, View ORCID ProfileVictor E. Reuter, View ORCID ProfileTimothy A. Chan, View ORCID ProfileEmily H. Cheng, View ORCID ProfileDavid A. Scheinberg, View ORCID ProfileMing O. Li, View ORCID ProfileJames J. Hsieh, View ORCID ProfileChris Sander, View ORCID ProfileA. Ari Hakimi
doi: https://doi.org/10.1101/025908
Yasin Şenbabaoğlu
1Computational Biology Center
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  • For correspondence: msk.immune.decomposition@gmail.com
Andrew G. Winer
2Urology Service, Department of Surgery
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Ron S. Gejman
3Molecular Pharmacology and Chemistry Program
11Weill Cornell Medical College
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Ming Liu
4Immunology Program
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Augustin Luna
1Computational Biology Center
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Irina Ostrovnaya
5Department of Epidemiology and Biostatistics
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Nils Weinhold
1Computational Biology Center
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William Lee
1Computational Biology Center
6Department of Radiation Oncology
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Samuel D. Kaffenberger
2Urology Service, Department of Surgery
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Ying Bei Chen
7Department of Pathology
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Martin H. Voss
8Genitourinary Oncology, Department of Medicine
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Jonathan A. Coleman
2Urology Service, Department of Surgery
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Paul Russo
2Urology Service, Department of Surgery
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Victor E. Reuter
7Department of Pathology
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Timothy A. Chan
6Department of Radiation Oncology
9Human Oncology & Pathogenesis Program
11Weill Cornell Medical College
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Emily H. Cheng
7Department of Pathology
9Human Oncology & Pathogenesis Program
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David A. Scheinberg
3Molecular Pharmacology and Chemistry Program
10Department of Medicine
11Weill Cornell Medical College
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Ming O. Li
4Immunology Program
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James J. Hsieh
8Genitourinary Oncology, Department of Medicine
9Human Oncology & Pathogenesis Program
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Chris Sander
1Computational Biology Center
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  • For correspondence: msk.immune.decomposition@gmail.com
A. Ari Hakimi
1Computational Biology Center
2Urology Service, Department of Surgery
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  • For correspondence: msk.immune.decomposition@gmail.com
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Abstract

One sentence summary In silico decomposition of the immune microenvironment among common tumor types identified clear cell renal cell carcinoma as the most highly infiltrated by T-cells and further analysis of this tumor type revealed three distinct and clinically relevant clusters which were validated in an independent cohort.

Abstract Infiltrating T cells in the tumor microenvironment have crucial roles in the competing processes of pro-tumor and anti-tumor immune response. However, the infiltration level of distinct T cell subsets and the signals that draw them into a tumor, such as the expression of antigen presenting machinery (APM) genes, remain poorly characterized across human cancers. Here, we define a novel mRNA-based T cell infiltration score (TIS) and profile infiltration levels in 19 tumor types. We find that clear cell renal cell carcinoma (ccRCC) is the highest for TIS and among the highest for the correlation between TIS and APM expression, despite a modest mutation burden. This finding is contrary to the expectation that immune infiltration and mutation burden are linked. To further characterize the immune infiltration in ccRCC, we use RNA-seq data to computationally infer the infiltration levels of 24 immune cell types in a discovery cohort of 415 ccRCC patients and validate our findings in an independent cohort of 101 ccRCC patients. We find three clusters of tumors that are primarily separated by levels of T cell infiltration and APM gene expression. In ccRCC, the levels of Th17 cells and the ratio of CD8+ T/Treg levels are associated with improved survival whereas the levels of Th2 cells and Tregs are associated with negative clinical outcome. Our analysis illustrates the utility of computational immune cell decomposition for solid tumors, and the potential of this method to guide clinical decision-making.

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Posted September 01, 2015.
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The landscape of T cell infiltration in human cancer and its association with antigen presenting gene expression
Yasin Şenbabaoğlu, Andrew G. Winer, Ron S. Gejman, Ming Liu, Augustin Luna, Irina Ostrovnaya, Nils Weinhold, William Lee, Samuel D. Kaffenberger, Ying Bei Chen, Martin H. Voss, Jonathan A. Coleman, Paul Russo, Victor E. Reuter, Timothy A. Chan, Emily H. Cheng, David A. Scheinberg, Ming O. Li, James J. Hsieh, Chris Sander, A. Ari Hakimi
bioRxiv 025908; doi: https://doi.org/10.1101/025908
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The landscape of T cell infiltration in human cancer and its association with antigen presenting gene expression
Yasin Şenbabaoğlu, Andrew G. Winer, Ron S. Gejman, Ming Liu, Augustin Luna, Irina Ostrovnaya, Nils Weinhold, William Lee, Samuel D. Kaffenberger, Ying Bei Chen, Martin H. Voss, Jonathan A. Coleman, Paul Russo, Victor E. Reuter, Timothy A. Chan, Emily H. Cheng, David A. Scheinberg, Ming O. Li, James J. Hsieh, Chris Sander, A. Ari Hakimi
bioRxiv 025908; doi: https://doi.org/10.1101/025908

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