title: Favorable prognostic influence of T-box transcription factor Eomesodermin in metastatic renal cell cancer patients.
abstract: T-box transcription factors, T-box expressed in T cells (T-bet) encoded by Tbx21 and Eomesodermin (Eomes), drive the differentiation of effector/memory T cell lineages and NK cells. The aim of the study was to determine the prognostic influence of the expression of these transcription factors in peripheral blood (pB) in a cohort of 41 metastatic (m) RCC patients before receiving sorafenib treatment and to analyze their association with the immunophenotype in pB. In contrast to Tbx21, in the multivariate analysis including clinical features, Eomes mRNA expression was identified as an independent good prognostic factor for progression-free survival (PFS, p = 0.042) and overall survival (OS, p = 0.001) in addition to a favorable ECOG performance status (p = 0.01 and p = 0.008, respectively). Eomes expression correlated positively not only with expression of Tbx21 and TGFβ1 mRNA, but also with mRNA expression of the activation marker ICOS, and with in vivo activated HLA-DR(+) T cells. Eomes expression was negatively associated with TNFα-producing T cells. On protein level, Eomes was mainly expressed by CD56(+)CD3(-) NK cells in pB. In conclusion, we identified a higher Eomes mRNA expression as an independent good prognostic factor for OS and PFS in mRCC patients treated with sorafenib.
authors.affiliation: Department of Medicine III (Hematology, Oncology and Tumor Immunology), Charité, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Dielmann
authors.affiliation: Department of Medicine III (Hematology, Oncology and Tumor Immunology), Charité, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Letsch
authors.affiliation: Department of Medicine III (Hematology, Oncology and Tumor Immunology), Charité, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany.
authors.forename: Anika
authors.initials: A
authors.lastname: Nonnenmacher
authors.affiliation: Department of Urology, Charité, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Kurt
authors.initials: K
authors.lastname: Miller
authors.affiliation: Department of Medicine III (Hematology, Oncology and Tumor Immunology), Charité, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Keilholz
authors.affiliation: Department of Medicine III (Hematology, Oncology and Tumor Immunology), Charité, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany. antonia.busse@charite.de.
authors.forename: Antonia
authors.initials: A
authors.lastname: Busse
mesh_terms: D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000401:mortality* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016130:Immunophenotyping; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000401:mortality* / Q000473:pathology; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D000098815:T-bet Transcription Factor
chemical_list: C491199:EOMES protein, human; D012333:RNA, Messenger; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor
keywords: Effector T cells; Eomesodermin; Memory T cells; Natural killer cells; Renal cell carcinoma; T-box expressed in T cells