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Up-regulation of indoleamine 2,3-dioxygenase 1(IDO1)expression and catalytic activity is associated with immunosuppression and poor prognosis in penile squamous cell carcinoma patients

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Cancer Communications 2020年第1期40卷 3-15页

作者： Qiang-hua Zhou Hui Han Jia-bin Lu ting-yu Liu Kang-bo Huang Chuang-zhong Deng Zai-shang Li Jie-ping Chen Kai Yao Zi-ke Qin Zhuo-wei Liu Yong-hong Li Sheng-jie Guo Yun-lin Ye Fang-jian Zhou Ran-yi Liu Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center of Cancer MedicineGuangzhouGuangdong510060 P.R.China Department of Urology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouGuangdong 510120P.R.China Department of Urology Sun Yat-sen University Cancer CenterGuangzhouGuangdong 510060P.R.China Department of Pathology Sun Yat-sen University Cancer CenterGuangzhouGuangdong 510060P.R.China Department of Urology Shenzhen People’s HospitalJinan UniversityShenzhenGuangdong 518021P.R.China

Background: Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan (trp)catabolism have been demonstrated to play an important role in tumor immunosuppression. this study examined the expression and catalytic activity of IDO1 in penilesquamous cell carcinoma (PSCC) and explored their clinical ***: IDO1 expression level, serum concentrations of trp and kynurenine (Kyn)were examined in 114 PSCC patients by immunohistonchemistry and solid-phaseextraction-liquid chromatography-tandem mass spectrometry. the survival was analyzed using Kaplan-Meier method and the log-rank test. Hazard ratio of death was analyzed via univariate and multivariate Cox regression. Immune cell types were definedby principal component analysis. the correlativity was assessed by Pearson’s correlation ***: the expression level of IDO1 in PSCC cells was positively correlatedwith serum Kyn concentration and Kyn/trp radio (KtR;both P t negatively correlated with serum trp concentration (P = 0.001). Additionally, IDO1 upregulation in cancer cells and the increase of serum KtR were significantly associated with advanced N stage (both P thologic grade (P = 0.008and 0.032, respectively). High expression level of IDO1 in cancer cells and serumKtR were associated with short disease-specific survival (both P tage (hazard radio [HR], 6.926;95% confidence interval [CI],2.458-19.068;P thologic grade (HR, 2.194;95% CI, 1.021-4.529;P = 0.038), only serum KtR (HR, 2.780;95% CI, 1.066-7.215;P = 0.036) was anindependent predictor for PSCC prognosis. IDO1 expression was positively correlated with the expression of interferon-𝛾 (IFN𝛾, P th protein 1, cytotoxic t-lymphocyte-associated protein 4 and programmed death-ligand 1 and 2;all P the infiltration ofimmune cells (including cytotoxic t lymphocytes, regulatory t lymphocytes, tumorassociated m

关键词： cytotoxic t-lymphocyte-associated protein 4 immunosuppression indoleamine 2 3-dioxygenase 1 interferon-gamma kynurenine/tryptophan ratio penile cancer programmed cell death protein 1 programmed death-ligand 1 tumor-infiltrating immune cells

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Faecal microbiota transplantation enhances efficacy of immune checkpoint inhibitors therapy against cancer

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World Journal of Gastroenterology 2021年第32期27卷 5362-5375页

作者： Yong-Bo Kang Yue Cai Department of Microbiology and Immunology School of Basic Medical SciencesShanxi Medical UniversityJinzhong 030600Shanxi ProvinceChina

Even though immune checkpoint inhibitors(ICIs)are effective on multiple cancer types,there are still many non-responding patients.A possible factor put forward that may influence the efficacy of ICIs is the gut ***,faecal microbiota transplantation may enhance efficacy of ***,the data available in this field are insufficient,and relevant scientific work has just *** a result,the current work reviewed the latest research on the association of gut microbiota with ICI treatments based on anti-programmed cell death protein 1 antibody and anti-cytotoxic t-lymphocyte-associated protein 4 antibody and explored the therapeutic potential of faecal microbiota transplantation in combination with ICI therapy in the future.

关键词： Gut microbiome Immunotherapy Programmed cell death protein 1/programmed cell death protein ligand 1 cytotoxic t-lymphocyte-associated protein 4 Immune checkpoint inhibitors resistance Faecal microbiota transplantation

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Blood and Histopathological Biomarkers of Immune-related Adverse Effects of treatment with Immune Checkpoint Inhibitors

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Journal of Nutritional Oncology 2019年第4期4卷 161-171页

作者： Yogesh Jheengut Yi Qian Liu Ling Xiang Liu Department of Oncology The First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China

Immune checkpoint inhibitors have been a recent major breakthrough in the management of *** have broadened the scope of management in medical oncology,which has been heavily dependent on *** checkpoint inhibitors have renewed the hope of many patients for a more effective ***,Immune checkpoint inhibitors are also associated with a variety of adverse effects,most commonly immunerelated adverse events,and these are often different from the known chemotherapy-induced ***,there is a need to identify specific biomarkers which are able to predict or diagnose these immune-related adverse events.

关键词： Immune checkpoint inhibitors Immune related adverse effects cytotoxic t-lymphocyte-associated protein 4 Programmed cell death-1 Programmed death-ligand 1

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Why natural killer cells in triple negative breast cancer?

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World Journal of Clinical Oncology 2020年第7期11卷 464-476页

作者： Mustafa Abdel-Latif Rana Ahmed Youness Biotechnology Program Faculty of Pharmacy and BiotechnologyGerman University in CairoCairo 11835Egypt Pharmaceutical Biology Department Faculty of Pharmacy and BiotechnologyGerman University in CairoCairo 11835Egypt

the triple-negative subtype of breast cancer(tNBC)has the bleakest prognosis,owing to its lack of either hormone receptor as well as human epidermal growth factor receptor ***,immunotherapy has emerged as the front-runner for tNBC treatment,which avoids potentially damaging ***,despite its documented association with aggressive side effects and developed resistance,immune checkpoint blockade continues to dominate the tNBC immunotherapy *** immune checkpoint blockade drawbacks necessitate the exploration of other immunotherapeutic methods that would expand options for tNBC *** such method is the exploitation and recruitment of natural killer cells,which by harnessing the innate rather than adaptive immune system could potentially circumvent the downsides of immune checkpoint *** this review,the authors will elucidate the advantageousness of natural killer cell-based immuno-oncology in tNBC as well as demonstrate the need to more extensively research such therapies in the future.

关键词： triple negative breast cancer Natural killer cells Immune checkpoint blockades Programmed death-ligand 1 cytotoxic t-lymphocyte-associated protein 4 Natural killer lectin-like group 2 member D

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