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01-06-2018 | Original Article

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

Published in: Cancer Microenvironment | Issue 1/2018

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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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Literature
1.
5.
14.
go back to reference Karja V, Aaltomaa S, Lipponen P, Isotalo T, Talja M, Mokka R (2005) Tumour-infiltrating lymphocytes: a prognostic factor of PSA-free survival in patients with local prostate carcinoma treated by radical prostatectomy. Anticancer Res 25(6C):4435–4438PubMed Karja V, Aaltomaa S, Lipponen P, Isotalo T, Talja M, Mokka R (2005) Tumour-infiltrating lymphocytes: a prognostic factor of PSA-free survival in patients with local prostate carcinoma treated by radical prostatectomy. Anticancer Res 25(6C):4435–4438PubMed
15.
go back to reference Vesalainen S, Lipponen P, Talja M, Syrjanen K (1994) Histological grade, perineural infiltration, tumour-infiltrating lymphocytes and apoptosis as determinants of long-term prognosis in prostatic adenocarcinoma. Eur J Cancer 30A(12):1797–1803CrossRefPubMed Vesalainen S, Lipponen P, Talja M, Syrjanen K (1994) Histological grade, perineural infiltration, tumour-infiltrating lymphocytes and apoptosis as determinants of long-term prognosis in prostatic adenocarcinoma. Eur J Cancer 30A(12):1797–1803CrossRefPubMed
16.
go back to reference Gao J, Ward JF, Pettaway CA, Shi LZ, Subudhi SK, Vence LM, Zhao H, Chen J, Chen H, Efstathiou E, Troncoso P, Allison JP, Logothetis CJ, Wistuba II, Sepulveda MA, Sun J, Wargo J, Blando J, Sharma P VISTA is an inhibitory immune checkpoint that is increased after ipilimumab therapy in patients with prostate cancer. Nat Med 2017;23(5):551–5. https://doi.org/10.1038/nm.4308, 555. Gao J, Ward JF, Pettaway CA, Shi LZ, Subudhi SK, Vence LM, Zhao H, Chen J, Chen H, Efstathiou E, Troncoso P, Allison JP, Logothetis CJ, Wistuba II, Sepulveda MA, Sun J, Wargo J, Blando J, Sharma P VISTA is an inhibitory immune checkpoint that is increased after ipilimumab therapy in patients with prostate cancer. Nat Med 2017;23(5):551–5. https://​doi.​org/​10.​1038/​nm.​4308, 555.
22.
go back to reference Wen L, Barber DF, Pao W, Wong FS, Owen MJ, Hayday A (1998) Primary gamma delta cell clones can be defined phenotypically and functionally as Th1/Th2 cells and illustrate the association of CD4 with Th2 differentiation. J Immunol 160(4):1965–1974PubMed Wen L, Barber DF, Pao W, Wong FS, Owen MJ, Hayday A (1998) Primary gamma delta cell clones can be defined phenotypically and functionally as Th1/Th2 cells and illustrate the association of CD4 with Th2 differentiation. J Immunol 160(4):1965–1974PubMed
23.
25.
go back to reference Seo N, Tokura Y, Takigawa M, Egawa K (1999) Depletion of IL-10- and TGF-beta-producing regulatory gamma delta T cells by administering a daunomycin-conjugated specific monoclonal antibody in early tumor lesions augments the activity of CTLs and NK cells. J Immunol 163(1):242–249PubMed Seo N, Tokura Y, Takigawa M, Egawa K (1999) Depletion of IL-10- and TGF-beta-producing regulatory gamma delta T cells by administering a daunomycin-conjugated specific monoclonal antibody in early tumor lesions augments the activity of CTLs and NK cells. J Immunol 163(1):242–249PubMed
Metadata
Title
Immunogenomics: A Negative Prostate Cancer Outcome Associated with TcR-γ/δ Recombinations
Publication date
01-06-2018
Published in
Cancer Microenvironment / Issue 1/2018
Print ISSN: 1875-2292
Electronic ISSN: 1875-2284
DOI
https://doi.org/10.1007/s12307-018-0204-6
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