PURPOSE: Tumor escape from host immune systems is a crucial mechanism for disease progression. We recently showed that the immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO) is a prognostic indicator for endometrial cancer. The purpose of the present study was to investigate the relationship between IDO expression and tumor-infiltrating lymphocytes (TIL) or natural killer (NK) cells and to clarify their prognostic effect in endometrial cancer. EXPERIMENTAL DESIGN: Immunohistochemical staining for IDO expression in endometrial cancer tissues (n = 65) was done. Tumor-infiltrating CD3+ and CD8+ lymphocytes, as well as CD57+ NK cells, were counted in serial tissue sections. RESULTS: High IDO expression in tumor cells was found in 32 of 65 cases and was positively correlated with myometrial invasion, nodal metastasis, and lymph-vascular space involvement. We also found a significant correlation between high IDO expression and reduced numbers of CD3+, CD8+, and CD57+ cells infiltrating into both the tumor epithelium and stroma. Patients with high IDO expression, a low number of stromal CD3 (<60), low intraepithelial CD8 (<25), or low stromal CD8 (<40) had significantly impaired progression-free survival. On multivariate analysis, IDO expression and the number of stromal CD3+ TILs were independent prognostic factors for impaired progression-free survival. CONCLUSIONS: Tumoral IDO expression correlated with a reduced number of TILs and NK cells in endometrial cancer, possibly contributing to disease progression and impaired clinical outcome. These findings suggest that targeting IDO to restore host antitumor immunity may be a therapeutic strategy for endometrial cancer.
PURPOSE:Tumor escape from host immune systems is a crucial mechanism for disease progression. We recently showed that the immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO) is a prognostic indicator for endometrial cancer. The purpose of the present study was to investigate the relationship between IDO expression and tumor-infiltrating lymphocytes (TIL) or natural killer (NK) cells and to clarify their prognostic effect in endometrial cancer. EXPERIMENTAL DESIGN: Immunohistochemical staining for IDO expression in endometrial cancer tissues (n = 65) was done. Tumor-infiltrating CD3+ and CD8+ lymphocytes, as well as CD57+ NK cells, were counted in serial tissue sections. RESULTS: High IDO expression in tumor cells was found in 32 of 65 cases and was positively correlated with myometrial invasion, nodal metastasis, and lymph-vascular space involvement. We also found a significant correlation between high IDO expression and reduced numbers of CD3+, CD8+, and CD57+ cells infiltrating into both the tumor epithelium and stroma. Patients with high IDO expression, a low number of stromal CD3 (<60), low intraepithelial CD8 (<25), or low stromal CD8 (<40) had significantly impaired progression-free survival. On multivariate analysis, IDO expression and the number of stromal CD3+ TILs were independent prognostic factors for impaired progression-free survival. CONCLUSIONS: Tumoral IDO expression correlated with a reduced number of TILs and NK cells in endometrial cancer, possibly contributing to disease progression and impaired clinical outcome. These findings suggest that targeting IDO to restore host antitumor immunity may be a therapeutic strategy for endometrial cancer.
Authors: Shona Hendry; Roberto Salgado; Thomas Gevaert; Prudence A Russell; Tom John; Bibhusal Thapa; Michael Christie; Koen van de Vijver; M V Estrada; Paula I Gonzalez-Ericsson; Melinda Sanders; Benjamin Solomon; Cinzia Solinas; Gert G G M Van den Eynden; Yves Allory; Matthias Preusser; Johannes Hainfellner; Giancarlo Pruneri; Andrea Vingiani; Sandra Demaria; Fraser Symmans; Paolo Nuciforo; Laura Comerma; E A Thompson; Sunil Lakhani; Seong-Rim Kim; Stuart Schnitt; Cecile Colpaert; Christos Sotiriou; Stefan J Scherer; Michail Ignatiadis; Sunil Badve; Robert H Pierce; Giuseppe Viale; Nicolas Sirtaine; Frederique Penault-Llorca; Tomohagu Sugie; Susan Fineberg; Soonmyung Paik; Ashok Srinivasan; Andrea Richardson; Yihong Wang; Ewa Chmielik; Jane Brock; Douglas B Johnson; Justin Balko; Stephan Wienert; Veerle Bossuyt; Stefan Michiels; Nils Ternes; Nicole Burchardi; Stephen J Luen; Peter Savas; Frederick Klauschen; Peter H Watson; Brad H Nelson; Carmen Criscitiello; Sandra O'Toole; Denis Larsimont; Roland de Wind; Giuseppe Curigliano; Fabrice André; Magali Lacroix-Triki; Mark van de Vijver; Federico Rojo; Giuseppe Floris; Shahinaz Bedri; Joseph Sparano; David Rimm; Torsten Nielsen; Zuzana Kos; Stephen Hewitt; Baljit Singh; Gelareh Farshid; Sibylle Loibl; Kimberly H Allison; Nadine Tung; Sylvia Adams; Karen Willard-Gallo; Hugo M Horlings; Leena Gandhi; Andre Moreira; Fred Hirsch; Maria V Dieci; Maria Urbanowicz; Iva Brcic; Konstanty Korski; Fabien Gaire; Hartmut Koeppen; Amy Lo; Jennifer Giltnane; Marlon C Rebelatto; Keith E Steele; Jiping Zha; Kenneth Emancipator; Jonathan W Juco; Carsten Denkert; Jorge Reis-Filho; Sherene Loi; Stephen B Fox Journal: Adv Anat Pathol Date: 2017-11 Impact factor: 3.875
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Authors: M Cavia-Saiz; P Muñiz Rodríguez; B Llorente Ayala; M García-González; M J Coma-Del Corral; C García Girón Journal: Mol Biol Rep Date: 2014-01-17 Impact factor: 2.316
Authors: A W L Bayci; D A Baker; A E Somerset; O Turkoglu; Z Hothem; R E Callahan; R Mandal; B Han; T Bjorndahl; D Wishart; R Bahado-Singh; S F Graham; R Keidan Journal: Metabolomics Date: 2018-08-03 Impact factor: 4.290