Prognostic Value of Tumor-Infiltrating Lymphocytes and Tertiary Lymphoid Structures in Epstein-Barr Virus-Associated and -Negative Gastric Carcinoma

BackgroundTumor-infiltrating lymphocytes (TILs) are considered a manifestation of the host immune response against cancer and tertiary lymphoid structures (TLS) may contribute to lymphocytes recruitment. Both of them have been reported as potential prognostic parameters in some human malignancies. H...

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Main Authors: Na Cheng, Peng Li, Huanhuan Cheng, Xiaoxiao Zhao, Min Dong, Yiwang Zhang, Peizhen Zhao, Jianning Chen, Chunkui Shao
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-07-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2021.692859/full
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author Na Cheng
Peng Li
Huanhuan Cheng
Xiaoxiao Zhao
Xiaoxiao Zhao
Min Dong
Yiwang Zhang
Peizhen Zhao
Jianning Chen
Chunkui Shao
author_facet Na Cheng
Peng Li
Huanhuan Cheng
Xiaoxiao Zhao
Xiaoxiao Zhao
Min Dong
Yiwang Zhang
Peizhen Zhao
Jianning Chen
Chunkui Shao
author_sort Na Cheng
collection DOAJ
description BackgroundTumor-infiltrating lymphocytes (TILs) are considered a manifestation of the host immune response against cancer and tertiary lymphoid structures (TLS) may contribute to lymphocytes recruitment. Both of them have been reported as potential prognostic parameters in some human malignancies. However, the roles of TILs, TLS, and their correlation in Epstein-Barr Virus-associated gastric carcinoma (EBVaGC) and EBV-negative gastric carcinoma (EBVnGC) are largely unknown.MethodsTo observe the correlation among TILs, TLS, and clinicopathological characteristics and their prognostic significance in EBVaGC and EBVnGC, respectively. TILs and TLS were assessed by morphology and/or immunohistochemistry, and accompanied by clinicopathological analysis from 846 gastric cancer patients in multiple institutions.ResultsForty-two (5.0%) cases of EBVaGC and 804 cases of EBVnGC were identified by in situ hybridization, respectively. For EBVnGC, higher TILs grade was correlated with TLS-present. EBVnGC patients with high TILs grade and TLS-present exhibited survival benefits. TILs (P = 0.001) and TLS (P = 0.003), especially TILs & TLS (P < 0.001) were independent prognostic factors in EBVnGC. A nomogram was constructed and validated for predicting the probability of overall survival and performed well with a good calibration. No significant prognostic value was detected in EBVaGC.ConclusionTILs and TLS, especially TILs & TLS were promising prognostic indicators for overall survival in EBVnGC. TILs and TLS were highly overlapping in their extent and prognostic abilities, and may be considered as a coindicator of prognosis of gastric cancer. The evaluations of TILs and TLS are simple and can be assessed routinely in pathological diagnosis.
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spelling doaj.art-0228829b33c041ca94986ef5410ef4892022-12-21T20:32:56ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-07-011210.3389/fimmu.2021.692859692859Prognostic Value of Tumor-Infiltrating Lymphocytes and Tertiary Lymphoid Structures in Epstein-Barr Virus-Associated and -Negative Gastric CarcinomaNa Cheng0Peng Li1Huanhuan Cheng2Xiaoxiao Zhao3Xiaoxiao Zhao4Min Dong5Yiwang Zhang6Peizhen Zhao7Jianning Chen8Chunkui Shao9Department of Pathology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaDepartment of Histology and Embryology of Basic Medical Department, Guangdong Medical University, Dongguan, ChinaDepartment of Ophthalmology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaDepartment of Pathology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaDepartment of Pathology, The Central Hospital of Wuhan, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Medical Oncology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaDepartment of Pathology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaDermatology Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Pathology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaDepartment of Pathology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaBackgroundTumor-infiltrating lymphocytes (TILs) are considered a manifestation of the host immune response against cancer and tertiary lymphoid structures (TLS) may contribute to lymphocytes recruitment. Both of them have been reported as potential prognostic parameters in some human malignancies. However, the roles of TILs, TLS, and their correlation in Epstein-Barr Virus-associated gastric carcinoma (EBVaGC) and EBV-negative gastric carcinoma (EBVnGC) are largely unknown.MethodsTo observe the correlation among TILs, TLS, and clinicopathological characteristics and their prognostic significance in EBVaGC and EBVnGC, respectively. TILs and TLS were assessed by morphology and/or immunohistochemistry, and accompanied by clinicopathological analysis from 846 gastric cancer patients in multiple institutions.ResultsForty-two (5.0%) cases of EBVaGC and 804 cases of EBVnGC were identified by in situ hybridization, respectively. For EBVnGC, higher TILs grade was correlated with TLS-present. EBVnGC patients with high TILs grade and TLS-present exhibited survival benefits. TILs (P = 0.001) and TLS (P = 0.003), especially TILs & TLS (P < 0.001) were independent prognostic factors in EBVnGC. A nomogram was constructed and validated for predicting the probability of overall survival and performed well with a good calibration. No significant prognostic value was detected in EBVaGC.ConclusionTILs and TLS, especially TILs & TLS were promising prognostic indicators for overall survival in EBVnGC. TILs and TLS were highly overlapping in their extent and prognostic abilities, and may be considered as a coindicator of prognosis of gastric cancer. The evaluations of TILs and TLS are simple and can be assessed routinely in pathological diagnosis.https://www.frontiersin.org/articles/10.3389/fimmu.2021.692859/fulltumor-infiltrating lymphocytestertiary lymphoid structuresEBV-associated gastric carcinomaEBV-negative gastric carcinomanomogramprognosis
spellingShingle Na Cheng
Peng Li
Huanhuan Cheng
Xiaoxiao Zhao
Xiaoxiao Zhao
Min Dong
Yiwang Zhang
Peizhen Zhao
Jianning Chen
Chunkui Shao
Prognostic Value of Tumor-Infiltrating Lymphocytes and Tertiary Lymphoid Structures in Epstein-Barr Virus-Associated and -Negative Gastric Carcinoma
Frontiers in Immunology
tumor-infiltrating lymphocytes
tertiary lymphoid structures
EBV-associated gastric carcinoma
EBV-negative gastric carcinoma
nomogram
prognosis
title Prognostic Value of Tumor-Infiltrating Lymphocytes and Tertiary Lymphoid Structures in Epstein-Barr Virus-Associated and -Negative Gastric Carcinoma
title_full Prognostic Value of Tumor-Infiltrating Lymphocytes and Tertiary Lymphoid Structures in Epstein-Barr Virus-Associated and -Negative Gastric Carcinoma
title_fullStr Prognostic Value of Tumor-Infiltrating Lymphocytes and Tertiary Lymphoid Structures in Epstein-Barr Virus-Associated and -Negative Gastric Carcinoma
title_full_unstemmed Prognostic Value of Tumor-Infiltrating Lymphocytes and Tertiary Lymphoid Structures in Epstein-Barr Virus-Associated and -Negative Gastric Carcinoma
title_short Prognostic Value of Tumor-Infiltrating Lymphocytes and Tertiary Lymphoid Structures in Epstein-Barr Virus-Associated and -Negative Gastric Carcinoma
title_sort prognostic value of tumor infiltrating lymphocytes and tertiary lymphoid structures in epstein barr virus associated and negative gastric carcinoma
topic tumor-infiltrating lymphocytes
tertiary lymphoid structures
EBV-associated gastric carcinoma
EBV-negative gastric carcinoma
nomogram
prognosis
url https://www.frontiersin.org/articles/10.3389/fimmu.2021.692859/full
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