PMID- 32536910 OWN - NLM STAT- MEDLINE DCOM- 20210315 LR - 20211108 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 11 DP - 2020 TI - Indoleamine 2,3-Dioxygenase 2 Immunohistochemical Expression in Resected Human Non-small Cell Lung Cancer: A Potential New Prognostic Tool. PG - 839 LID - 10.3389/fimmu.2020.00839 [doi] LID - 839 AB - Indoleamine 2,3-dioxygenase 2 (IDO2) is an analog of the tryptophan degrading and immunomodulating enzyme indoleamine 2,3-dioxygenase 1 (IDO1). Although the role of IDO1 is largely understood, the function of IDO2 is not yet well-elucidated. IDO2 overexpression was documented in some human tumors, but the linkage between IDO2 expression and cancer progression is still unclear, in particular in non-small cell lung cancer (NSCLC). Immunohistochemical expression and cellular localization of IDO2 was evaluated on 191 formalin-fixed and paraffin-embedded resected NSCLC. Correlations between IDO2 expression, clinical-pathological data, tumor-infiltrating lymphocytes (TILs), immunosuppressive tumor molecules (IDO1 and programmed cell death ligand-1 - PD-L1 -) and patients' prognosis were evaluated. IDO2 high expression is strictly related to high PD-L1 level among squamous cell carcinomas group (p = 0.012), to either intratumoral or mixed localization of TILs (p < 0.001) and to adenocarcinoma histotype (p < 0.001). Furthermore, a significant correlation between IDO2 high expression and poor non-small cell lung cancer prognosis was detected (p = 0.011). The current study reaches interesting knowledge about IDO2 in non-small cell lung cancer. The close relationship between IDO2 expression, PD-L1 increased levels, TILs localization and NSCLC poor prognosis, assumed IDO2 as a potential prognostic biomarker to be exploited for optimizing innovative combined therapies with immune checkpoint inhibitors. CI - Copyright (c) 2020 Mandarano, Bellezza, Belladonna, Vannucci, Gili, Ferri, Lupi, Ludovini, Falabella, Metro, Mondanelli, Chiari, Cagini, Stracci, Roila, Puma, Volpi and Sidoni. FAU - Mandarano, Martina AU - Mandarano M AD - Section of Anatomic Pathology and Histology, Department of Experimental Medicine, Medical School, University of Perugia, Perugia, Italy. FAU - Bellezza, Guido AU - Bellezza G AD - Section of Anatomic Pathology and Histology, Department of Experimental Medicine, Medical School, University of Perugia, Perugia, Italy. FAU - Belladonna, Maria Laura AU - Belladonna ML AD - Section of Pharmacology, Department of Experimental Medicine, University of Perugia, Perugia, Italy. FAU - Vannucci, Jacopo AU - Vannucci J AD - Department of Thoracic Surgery, Medical School, University of Perugia, Perugia, Italy. FAU - Gili, Alessio AU - Gili A AD - Section of Public Health, Department of Experimental Medicine, University of Perugia, Perugia, Italy. FAU - Ferri, Ivana AU - Ferri I AD - Section of Anatomic Pathology and Histology, Department of Experimental Medicine, Medical School, University of Perugia, Perugia, Italy. FAU - Lupi, Chiara AU - Lupi C AD - Umbria Cancer Registry, Perugia, Italy. FAU - Ludovini, Vienna AU - Ludovini V AD - Department of Medical Oncology, Santa Maria della Misericordia Hospital, Perugia, Italy. FAU - Falabella, Giulia AU - Falabella G AD - Section of Anatomic Pathology and Histology, Department of Experimental Medicine, Medical School, University of Perugia, Perugia, Italy. FAU - Metro, Giulio AU - Metro G AD - Department of Medical Oncology, Santa Maria della Misericordia Hospital, Perugia, Italy. FAU - Mondanelli, Giada AU - Mondanelli G AD - Section of Pharmacology, Department of Experimental Medicine, University of Perugia, Perugia, Italy. FAU - Chiari, Rita AU - Chiari R AD - Medical Oncology, Ospedali Riuniti Padova sud, Padova, Italy. FAU - Cagini, Lucio AU - Cagini L AD - Department of Thoracic Surgery, Medical School, University of Perugia, Perugia, Italy. FAU - Stracci, Fabrizio AU - Stracci F AD - Section of Public Health, Department of Experimental Medicine, University of Perugia, Perugia, Italy. AD - Umbria Cancer Registry, Perugia, Italy. FAU - Roila, Fausto AU - Roila F AD - Department of Medical Oncology, Santa Maria della Misericordia Hospital, Perugia, Italy. FAU - Puma, Francesco AU - Puma F AD - Department of Thoracic Surgery, Medical School, University of Perugia, Perugia, Italy. FAU - Volpi, Claudia AU - Volpi C AD - Section of Pharmacology, Department of Experimental Medicine, University of Perugia, Perugia, Italy. FAU - Sidoni, Angelo AU - Sidoni A AD - Section of Anatomic Pathology and Histology, Department of Experimental Medicine, Medical School, University of Perugia, Perugia, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200527 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (B7-H1 Antigen) RN - 0 (Biomarkers, Tumor) RN - 0 (CD274 protein, human) RN - 0 (IDO1 protein, human) RN - 0 (IDO2 protein, human) RN - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase) SB - IM MH - Adenocarcinoma/*metabolism/pathology/surgery MH - Adult MH - Aged MH - Aged, 80 and over MH - B7-H1 Antigen/metabolism MH - Biomarkers, Tumor/metabolism MH - Carcinoma, Non-Small-Cell Lung/*metabolism/pathology/surgery MH - Carcinoma, Squamous Cell/*metabolism/pathology/surgery MH - Disease Progression MH - Female MH - Follow-Up Studies MH - Humans MH - Immunohistochemistry/*methods MH - Indoleamine-Pyrrole 2,3,-Dioxygenase/*metabolism MH - Lung Neoplasms/*metabolism/pathology/surgery MH - Lymphocytes, Tumor-Infiltrating/immunology MH - Male MH - Middle Aged MH - Prognosis PMC - PMC7267213 OTO - NOTNLM OT - 3-dioxygenase 2 OT - biomarker OT - immunohistochemistry OT - immunomodulator OT - indoleamine 2 OT - non-small cell lung cancer EDAT- 2020/06/17 06:00 MHDA- 2021/03/16 06:00 PMCR- 2020/01/01 CRDT- 2020/06/16 06:00 PHST- 2020/01/09 00:00 [received] PHST- 2020/04/14 00:00 [accepted] PHST- 2020/06/16 06:00 [entrez] PHST- 2020/06/17 06:00 [pubmed] PHST- 2021/03/16 06:00 [medline] PHST- 2020/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2020.00839 [doi] PST - epublish SO - Front Immunol. 2020 May 27;11:839. doi: 10.3389/fimmu.2020.00839. eCollection 2020.