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Immunogenomics: A Negative Prostate Cancer Outcome Associated with TcR-γ/δ Recombinations

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Cancer Microenvironment

Abstract

We developed a scripted algorithm, based on previous, earlier editions of the algorithm, to mine prostate cancer exome files for T-cell receptor (TcR) recombination reads: Reads representing TcR gene recombinations were identified in 497 prostate cancer exome files from the cancer genome atlas (TCGA). As has been reported for melanoma, co-detection of productive TcR-α and TcR-β recombination reads correlated with an RNA expression signature representing T-cell exhaustion, particularly with high RNA levels for PD-1 and PD-L1, in comparison to several different control sets of samples. Co-detection of TcR-α and TcR-β recombination reads also correlated with high level expression of genes representing antigen presenting functions, further supporting the conclusion that co-detection of TcR-α and TcR-β recombination reads represents an immunologically relevant microenvironment. Finally, detection of unproductive TcR-δ recombinations, and unproductive and productive TcR-γ recombinations, strongly correlated with, and may represent a convenient biomarker for a poor clinical outcome. These results underscore the value of the genomics-based assessment of unproductive TcR recombinations and raise questions about the impact of tumor microenvironment lymphocytes in the absence of antigenicity.

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Acknowledgements

Authors thank USF research computing and the taxpayers of the State of Florida. This article is dedicated to William.

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Authors and Affiliations

  1. Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL, 33612, USA

    Yaping N. Tu, Wei Lue Tong, John M. Yavorski & George Blanck

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  1. Yaping N. Tu
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  2. Wei Lue Tong
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  3. John M. Yavorski
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Correspondence to George Blanck.

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Tu, Y.N., Tong, W.L., Yavorski, J.M. et al. Immunogenomics: A Negative Prostate Cancer Outcome Associated with TcR-γ/δ Recombinations. Cancer Microenvironment 11, 41–49 (2018). https://doi.org/10.1007/s12307-018-0204-6

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  • DOI: https://doi.org/10.1007/s12307-018-0204-6

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