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Myungwoo Nam Department of Medicine, Lincoln Medical and Mental Health Center, Bronx, New York, USA

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Woojung Yang Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA

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Hye Sung Kim Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA

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Jewel Park Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA

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Gahee Park Lunit Inc, Oncology group, Seoul, Republic of Korea

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Sukjun Kim Lunit Inc, Oncology group, Seoul, Republic of Korea

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Sanghoon Song Lunit Inc, Oncology group, Seoul, Republic of Korea

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Chan-Young Ock Lunit Inc, Oncology group, Seoul, Republic of Korea

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Victor G Wang Department of Genetics and Genome Sciences, UConn Health, Farmington, Connecticut, USA
The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA

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Jeffrey H Chuang Department of Genetics and Genome Sciences, UConn Health, Farmington, Connecticut, USA
The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA

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Young Kwang Chae Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA

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(TCGA) PTC cohort and classified tumors into three immune phenotypes (IPs). Our study is the first to investigate the implications of IP classification in PTC utilizing TILs via a tissue-based approach. Our study aimed to gain a better understanding of

Article Type:
Research Article
DOI:
https://doi.org/10.1530/ERC-23-0110
Volume/Issue:
Volume 30: Issue 9
Restricted access
Vivian Rosery Bridge Institute of Experimental Tumor Therapy, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

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Henning Reis Institute of Pathology, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

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Konstantinos Savvatakis Bridge Institute of Experimental Tumor Therapy, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK), Partner site University Hospital Essen, and German Cancer Research Center (DKFZ), Heidelberg, Germany

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Bernd Kowall Center of Clinical Epidemiology, Institute for Medical Informatics, Biometry and Epidemiology, Medical Faculty, University Duisburg-Essen, Essen, Germany

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Martin Stuschke Department of Radiotherapy, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
German Cancer Consortium (DKTK), Partner site University Hospital Essen, Essen, Germany

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Andreas Paul German Cancer Consortium (DKTK), Partner site University Hospital Essen, Essen, Germany
General, Visceral and Transplantation Surgery, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

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Alexander Dechêne Department of Gastroenterology and Hepatology, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
Department of Internal Medicine 6, Paracelsus Medical University, Nürnberg, Germany

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JiaJin Yang Bridge Institute of Experimental Tumor Therapy, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK), Partner site University Hospital Essen, and German Cancer Research Center (DKFZ), Heidelberg, Germany

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Ben Zhao Bridge Institute of Experimental Tumor Therapy, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK), Partner site University Hospital Essen, and German Cancer Research Center (DKFZ), Heidelberg, Germany

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Arianna Borgers Bridge Institute of Experimental Tumor Therapy, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK), Partner site University Hospital Essen, and German Cancer Research Center (DKFZ), Heidelberg, Germany

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Stefan Kasper Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
German Cancer Consortium (DKTK), Partner site University Hospital Essen, Essen, Germany

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Martin Schuler Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
German Cancer Consortium (DKTK), Partner site University Hospital Essen, Essen, Germany

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Phyllis F Cheung Bridge Institute of Experimental Tumor Therapy, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK), Partner site University Hospital Essen, and German Cancer Research Center (DKFZ), Heidelberg, Germany

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Jens T Siveke Bridge Institute of Experimental Tumor Therapy, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK), Partner site University Hospital Essen, and German Cancer Research Center (DKFZ), Heidelberg, Germany
German Cancer Consortium (DKTK), Partner site University Hospital Essen, Essen, Germany

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The tumor immune microenvironment (TME) represents a key determinant for responses to cancer treatment. However, the immune phenotype of highly proliferative gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) is still largely elusive. In this retrospective study, we characterized the TME of high-grade (G3, Ki-67 > 20%) GEP-NEN. We analyzed formalin-fixed paraffin-embedded samples from 37 patients with GEP-NEN G3 by immunohistochemistry and multiplex immunofluorescence to address the abundance and spatial interaction of relevant immune subsets. We focused on the expression of immune checkpoint molecules PD-1 and PD-L1, the cytotoxic T-cell marker CD8, and the tumor-associated macrophage marker CD206. Findings were correlated with overall survival (OS) from the date of a cancer diagnosis. Patients with PD-L1-positive tumors (CPS ≥ 1) and intense PD-1+CD8+ immune cell infiltration showed the most favorable median OS. Multiplex immunofluorescence staining of ten representative tissue samples illustrated intratumoral heterogeneity of PD-L1 expression. Dense PD-1+CD8+ immune cell infiltrates were observed in PD-L1-positive tumor regions but not in PD-L1-negative regions. Proximity analysis revealed a spatial interaction between PD-1+CD8+ cells and PD-L1-positive cells. Our data suggest a pre-existing antitumor immune response in the TME in a subgroup of GEP-NEN G3. This supports a targeted clinical exploration of immunotherapeutic approaches.

Article Type:
Research Article
DOI:
https://doi.org/10.1530/ERC-21-0223
Volume/Issue:
Volume 28: Issue 10
Restricted access
Francesca Coperchini Istituti Clinici Scientifici Maugeri IRCCS, Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, Pavia, Italy

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Laura Croce Istituti Clinici Scientifici Maugeri IRCCS, Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, Pavia, Italy
PHD Course in Experimental Medicine, University of Pavia, Pavia, Italy

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Michele Marinò Endocrinology Unit I, Department of Clinical and Experimental Medicine, University Hospital of Pisa, University of Pisa, Pisa, Italy

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Luca Chiovato Istituti Clinici Scientifici Maugeri IRCCS, Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, Pavia, Italy
Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy

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Mario Rotondi Istituti Clinici Scientifici Maugeri IRCCS, Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, Pavia, Italy
Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy

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Inflammation is currently regarded as an essential component of malignancies. It is now known that the tumor microenvironment may profoundly influence the biological behavior of cancer cells and ultimately the patient’s outcome. Chemokine and their receptor play a major role in determining the immune phenotype of the cells infiltrating the thyroid tumor microenvironment. Experimental evidence shows that both normal and cancer thyroid cells express specific chemokine receptors. The expression of at least some of these receptors exerts several biological effects, which influence the course of the disease. The present review article will take into account the role of the most studied chemokine receptors (CXCR1, CXCR2, CXCR3, CXCR4, CXCR7, DARC, CCR3, CCR6 and CCR7) in the context of thyroid cancer. This review will focus on current knowledge provided by in vitro and in vivo studies specifically performed on thyroid cancer including (i) expression of chemokine receptors in normal and cancer thyroid cells; (ii) role of chemokine receptors in affecting the biological behavior of thyroid tumors including the metastatic process; (iii) current knowledge about immunotherapies through targeting of chemokine receptors in thyroid cancer.

Article Type:
Review Article
DOI:
https://doi.org/10.1530/ERC-19-0163
Volume/Issue:
Volume 26: Issue 8
Free access
Lucas Leite Cunha Laboratory of Cancer Molecular Genetics, Laboratory of Cell Signaling, Department of Radiology, Adolfo Lutz Institute, Department of Pathology, Laboratory of Investigative and Molecular Pathology (Ciped), Faculty of Medical Sciences, University of Campinas (Unicamp), PO Box 6111, 126 Tessalia Vieira de Camargo Street, Campinas, São Paulo, Brazil

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Elaine Cristina Morari Laboratory of Cancer Molecular Genetics, Laboratory of Cell Signaling, Department of Radiology, Adolfo Lutz Institute, Department of Pathology, Laboratory of Investigative and Molecular Pathology (Ciped), Faculty of Medical Sciences, University of Campinas (Unicamp), PO Box 6111, 126 Tessalia Vieira de Camargo Street, Campinas, São Paulo, Brazil

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Ana Carolina Trindade Guihen Laboratory of Cancer Molecular Genetics, Laboratory of Cell Signaling, Department of Radiology, Adolfo Lutz Institute, Department of Pathology, Laboratory of Investigative and Molecular Pathology (Ciped), Faculty of Medical Sciences, University of Campinas (Unicamp), PO Box 6111, 126 Tessalia Vieira de Camargo Street, Campinas, São Paulo, Brazil

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Daniela Razolli Laboratory of Cancer Molecular Genetics, Laboratory of Cell Signaling, Department of Radiology, Adolfo Lutz Institute, Department of Pathology, Laboratory of Investigative and Molecular Pathology (Ciped), Faculty of Medical Sciences, University of Campinas (Unicamp), PO Box 6111, 126 Tessalia Vieira de Camargo Street, Campinas, São Paulo, Brazil

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Renê Gerhard Laboratory of Cancer Molecular Genetics, Laboratory of Cell Signaling, Department of Radiology, Adolfo Lutz Institute, Department of Pathology, Laboratory of Investigative and Molecular Pathology (Ciped), Faculty of Medical Sciences, University of Campinas (Unicamp), PO Box 6111, 126 Tessalia Vieira de Camargo Street, Campinas, São Paulo, Brazil

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Suely Nonogaki Laboratory of Cancer Molecular Genetics, Laboratory of Cell Signaling, Department of Radiology, Adolfo Lutz Institute, Department of Pathology, Laboratory of Investigative and Molecular Pathology (Ciped), Faculty of Medical Sciences, University of Campinas (Unicamp), PO Box 6111, 126 Tessalia Vieira de Camargo Street, Campinas, São Paulo, Brazil

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Fernando Augusto Soares Laboratory of Cancer Molecular Genetics, Laboratory of Cell Signaling, Department of Radiology, Adolfo Lutz Institute, Department of Pathology, Laboratory of Investigative and Molecular Pathology (Ciped), Faculty of Medical Sciences, University of Campinas (Unicamp), PO Box 6111, 126 Tessalia Vieira de Camargo Street, Campinas, São Paulo, Brazil

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José Vassallo Laboratory of Cancer Molecular Genetics, Laboratory of Cell Signaling, Department of Radiology, Adolfo Lutz Institute, Department of Pathology, Laboratory of Investigative and Molecular Pathology (Ciped), Faculty of Medical Sciences, University of Campinas (Unicamp), PO Box 6111, 126 Tessalia Vieira de Camargo Street, Campinas, São Paulo, Brazil

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Laura Sterian Ward Laboratory of Cancer Molecular Genetics, Laboratory of Cell Signaling, Department of Radiology, Adolfo Lutz Institute, Department of Pathology, Laboratory of Investigative and Molecular Pathology (Ciped), Faculty of Medical Sciences, University of Campinas (Unicamp), PO Box 6111, 126 Tessalia Vieira de Camargo Street, Campinas, São Paulo, Brazil

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Relationship between macrophages and the immune phenotype of inflammatory cells Tumor markers Immune cell markers Immune cells MUC1 ATM PTEN NIS B7-H1 CD56 FOXP3+ MDSCs Th17 CD20+ CD8+ CD4+ CD3+ Macrophages <0.0001 <0.0001 a NS NS <0.0001 NS <0.0001 NS NS 0

Article Type:
Research Article
DOI:
https://doi.org/10.1530/ERC-11-0285
Volume/Issue:
Volume 19: Issue 3
Free access
Lucas Leite Cunha Laboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Federal University of São Paulo, São Paulo, Brazil

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Laura Sterian Ward Laboratory of Cancer Molecular Genetics, Faculty of Medical Sciences, University of Campinas (Unicamp), Campinas, Brazil

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identified six different immune phenotypes of the microenvironment that could be clustered as wound healing, IFN-gamma dominant, inflammatory, lymphocyte depleted, immunologically quiet and TGF-beta dominant. They proceeded to integrate both genomic

Article Type:
Review Article
DOI:
https://doi.org/10.1530/ERC-21-0414
Volume/Issue:
Volume 29: Issue 6
Free access
Xiang Zhang Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China

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Ya Hu Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

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Ming Cui Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

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Mengyi Wang Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

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Xiaobin Li Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

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Yalu Zhang Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

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Sen Yang Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

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Surong Hua Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

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Meiping Shen Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China

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Quan Liao Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

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Biology 18 220. ( https://doi.org/10.1186/s13059-017-1349-1 ) Azizi E Carr AJ Plitas G Cornish AE Konopacki C Prabhakaran S Nainys J Wu K Kiseliovas V Setty M 2018 Single-cell map of diverse immune phenotypes in the breast tumor

Article Type:
Research Article
DOI:
https://doi.org/10.1530/ERC-22-0325
Volume/Issue:
Volume 30: Issue 3
Restricted access
Andrew McDonald Winship Cancer Institute at Emory University, Atlanta, Georgia, USA

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Vaidehi Avadhani Grady Memorial Hospital, Atlanta, Georgia, USA

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Gabriela Oprea-Ilies Grady Memorial Hospital, Atlanta, Georgia, USA

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Katerina Zakka Winship Cancer Institute at Emory University, Atlanta, Georgia, USA

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Gregory B Lesinski Winship Cancer Institute at Emory University, Atlanta, Georgia, USA

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Olumide B Gbolahan Winship Cancer Institute at Emory University, Atlanta, Georgia, USA

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Olatunji Alese Winship Cancer Institute at Emory University, Atlanta, Georgia, USA

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PF Dasari A Campbell KS & Vijayvergia N 2021 Impacts of pembrolizumab therapy on immune phenotype in patients with high-grade neuroendocrine neoplasms . Cancer Immunology, Immunotherapy 70 1893 – 1906 . ( https://doi.org/10.1007/s00262

Article Type:
Research Article
DOI:
https://doi.org/10.1530/ERC-24-0046
Volume/Issue:
Volume 31: Issue 10
Restricted access
J T W Kwon Department of Oncology, University of Oxford, Oxford, UK

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R J Bryant Department of Oncology, University of Oxford, Oxford, UK
Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK

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E E Parkes Department of Oncology, University of Oxford, Oxford, UK

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128 5137 – 5149 . ( https://doi.org/10.1172/JCI96268 ) Jenzer M Keß P Nientiedt C Endris V Kippenberger M Leichsenring J Stögbauer F Haimes J Mishkin S Kudlow B 2019 The BRCA2 mutation status shapes the immune phenotype of

Article Type:
Review Article
Collections:
Top-cited articles of 2023
DOI:
https://doi.org/10.1530/ERC-21-0149
Volume/Issue:
Volume 28: Issue 8
Open access
Sijin Li Department of Thyroid Surgery, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China

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Zhen Chen Department of Thyroid Surgery, Guangzhou First People’s Hospital, Guangzhou, China

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Mengchu Liu School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, China

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Liang Li Medical Research Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China

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Wensong Cai Department of Thyroid Surgery, Guangzhou First People’s Hospital, Guangzhou, China

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Zhe-Xiong Lian Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China

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Haixia Guan Department of Endocrinology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China

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Bo Xu Department of Thyroid Surgery, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China

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, including the immune phenotypes of PTC-infiltrating Tregs. In particular, we adopted bioinformatics analysis methods that are commonly used in single-cell RNA sequencing to analyze and present our flow cytometry data. We demonstrated that Treg cells are

Article Type:
Research Article
DOI:
https://doi.org/10.1530/ERC-23-0240
Volume/Issue:
Volume 31: Issue 3
Restricted access
Stephan Gasser Roche Pharma Research and Early Development, Roche Innovation Center Zurich, Roche Glycart AG, Schlieren, Switzerland
Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, NUS Immunology Programme, Centre for Life Sciences, National University of Singapore, Singapore

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Lina H K Lim Department of Physiology, Yong Loo Lin School of Medicine, NUS Immunology Programme, Centre for Life Sciences, National University of Singapore, Singapore

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Florence S G Cheung Department of Physiology, Yong Loo Lin School of Medicine, NUS Immunology Programme, Centre for Life Sciences, National University of Singapore, Singapore

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localisation within the tumour microenvironment are likely to impact the results ( Teng et al . 2015 , Chen & Mellman 2017 ). In an attempt to categorise cancers according to their immune phenotype, three broad types of cancer were suggested to exist

Article Type:
Review Article
DOI:
https://doi.org/10.1530/ERC-17-0146
Volume/Issue:
Volume 24: Issue 12
Free access