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Copyright © 2020 Xiao Wu et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. https://creativecommons.org/licenses/by/4.0/

Abstract

Primary esophageal small cell carcinoma (PESCC) is a weakly prevalent but lethal malignancy with early metastasis and a poor prognosis. Currently, neither effective prognostic indicators nor curative therapies are available for PESCC. Immunotherapy has now evolved into one of the most promising therapies for cancer patients. Tumor-infiltrating immune cells which are integral to the tumor immune microenvironment (TIME) are recognized as highly important for prognosis prediction, while the responsiveness to immune checkpoint blockade may be subject to the features of TIME. In this study, we aim to identify the TIME and provide indication for the applicability of immune checkpoint therapy in PESCC. We found that PD-L1 expression was detected in 33.33% (27/81) of all the patients, mostly exhibiting a stroma-only pattern and that it was positively associated with tumor-infiltrating immune cells (CD4+, CD8+, and CD163+). In 74.07% of PD-L1-positive specimens, PD-L1+CD163+ cells were colocalized more with CD4+ than CD8+ T cells. 83.95% (68/81) of all the specimens were infiltrated with more CD4+ than CD8+ T cells. Further analysis showed FoxP3+ Tregs constituted 13-27% of the total CD4+ T cell population. The Kaplan-–Meier analysis indicated several factors that contribute to poor survival, including negative PD-L1 expression, rich CD4 expression, rich FoxP3 expression, a low CD8/CD4 ratio, and a high FoxP3/CD8 ratio. A nomogram model was constructed and showed good performance for survival prediction. These results highlight that a suppressive TIME contributes to poor survival of patients with PESCC. TIME analyses might be a promising approach to evaluate the possibility and effect of immune checkpoint-based immunotherapeutics in PESCC patients.

Details

Title
Tumor-Infiltrating Immune Cells and PD-L1 as Prognostic Biomarkers in Primary Esophageal Small Cell Carcinoma
Author
Wu, Xiao 1 ; Ke, Xiurong 2 ; Ni, Yangpeng 3 ; Kuang, Liping 4 ; Zhang, Fan 5 ; Lin, Yusheng 6 ; Lin, Wan 1 ; Xiong, Xiao 7 ; Huang, Haihua 8 ; Lin, Xianjie 1 ; Zhang, Hao 9   VIAFID ORCID Logo 

 Cancer Research Center, Shantou University Medical College, Shantou, Guangdong, China 
 Cancer Research Center, Shantou University Medical College, Shantou, Guangdong, China; Department of Surgery, Laboratory for Translational Surgical Oncology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands 
 Department of Pathology, Jieyang People’s Hospital (Jieyang Affiliated Hospital, Sun Yat-Sen University), Jieyang, Guangdong, China 
 Department of Pathology, Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-Sen University, Shantou, Guangdong, China 
 Guangdong Provincial Key Laboratory for Breast Cancer Diagnosis and Treatment, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China 
 Cancer Research Center, Shantou University Medical College, Shantou, Guangdong, China; Department of Hematology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands 
 Department of General Surgery, The First Affiliated Hospital of Jinan University and Institute of Precision Cancer Medicine and Pathology, Jinan University Medical College, Guangzhou, Guangdong, China 
 Department of Pathology, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China 
 Department of General Surgery, The First Affiliated Hospital of Jinan University and Institute of Precision Cancer Medicine and Pathology, Jinan University Medical College, Guangzhou, Guangdong, China; Research Center of Translational Medicine, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China 
Editor
Vladimir Mulens
Publication year
2020
Publication date
2020
Publisher
John Wiley & Sons, Inc.
ISSN
23148861
e-ISSN
23147156
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2476481854
Copyright
Copyright © 2020 Xiao Wu et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. https://creativecommons.org/licenses/by/4.0/