Prognostic Value of Tumor-Infiltrating Lymphocytes and Tertiary Lymphoid Structures in Epstein-Barr Virus-Associated and -Negative Gastric Carcinoma
Tumor-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, th...
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| Published in | Frontiers in immunology Vol. 12; p. 692859 |
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| Main Authors | , , , , , , , , |
| Format | Journal Article |
| Language | English |
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01.07.2021
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| Abstract | Tumor-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.
To 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.
Forty-two (5.0%) cases of EBVaGC and 804 cases of EBVnGC were identified by
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 (
= 0.001) and TLS (
= 0.003), especially TILs & TLS (
< 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.
TILs 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. |
|---|---|
| AbstractList | Tumor-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.
To 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.
Forty-two (5.0%) cases of EBVaGC and 804 cases of EBVnGC were identified by
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 (
= 0.001) and TLS (
= 0.003), especially TILs & TLS (
< 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.
TILs 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. Tumor-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.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.To 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.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.Forty-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.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.TILs 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.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. 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. |
| Author | Cheng, Huanhuan Zhao, Xiaoxiao Dong, Min Shao, Chunkui Zhang, Yiwang Chen, Jianning Li, Peng Zhao, Peizhen Cheng, Na |
| AuthorAffiliation | 1 Department of Pathology, The Third Affiliated Hospital, Sun Yat-Sen University , Guangzhou , China 4 Department of Pathology, The Central Hospital of Wuhan, Huazhong University of Science and Technology , Wuhan , China 6 Dermatology Hospital, Southern Medical University , Guangzhou , China 2 Department of Histology and Embryology of Basic Medical Department, Guangdong Medical University , Dongguan , China 5 Department of Medical Oncology, The Third Affiliated Hospital, Sun Yat-Sen University , Guangzhou , China 3 Department of Ophthalmology, The Third Affiliated Hospital, Sun Yat-Sen University , Guangzhou , China |
| AuthorAffiliation_xml | – name: 3 Department of Ophthalmology, The Third Affiliated Hospital, Sun Yat-Sen University , Guangzhou , China – name: 2 Department of Histology and Embryology of Basic Medical Department, Guangdong Medical University , Dongguan , China – name: 1 Department of Pathology, The Third Affiliated Hospital, Sun Yat-Sen University , Guangzhou , China – name: 5 Department of Medical Oncology, The Third Affiliated Hospital, Sun Yat-Sen University , Guangzhou , China – name: 4 Department of Pathology, The Central Hospital of Wuhan, Huazhong University of Science and Technology , Wuhan , China – name: 6 Dermatology Hospital, Southern Medical University , Guangzhou , China |
| Author_xml | – sequence: 1 givenname: Na surname: Cheng fullname: Cheng, Na – sequence: 2 givenname: Peng surname: Li fullname: Li, Peng – sequence: 3 givenname: Huanhuan surname: Cheng fullname: Cheng, Huanhuan – sequence: 4 givenname: Xiaoxiao surname: Zhao fullname: Zhao, Xiaoxiao – sequence: 5 givenname: Min surname: Dong fullname: Dong, Min – sequence: 6 givenname: Yiwang surname: Zhang fullname: Zhang, Yiwang – sequence: 7 givenname: Peizhen surname: Zhao fullname: Zhao, Peizhen – sequence: 8 givenname: Jianning surname: Chen fullname: Chen, Jianning – sequence: 9 givenname: Chunkui surname: Shao fullname: Shao, Chunkui |
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| ContentType | Journal Article |
| Copyright | Copyright © 2021 Cheng, Li, Cheng, Zhao, Dong, Zhang, Zhao, Chen and Shao. Copyright © 2021 Cheng, Li, Cheng, Zhao, Dong, Zhang, Zhao, Chen and Shao 2021 Cheng, Li, Cheng, Zhao, Dong, Zhang, Zhao, Chen and Shao |
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| Keywords | tumor-infiltrating lymphocytes nomogram EBV-associated gastric carcinoma prognosis EBV-negative gastric carcinoma tertiary lymphoid structures |
| Language | English |
| License | Copyright © 2021 Cheng, Li, Cheng, Zhao, Dong, Zhang, Zhao, Chen and Shao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
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| Notes | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Undefined-3 These authors have contributed equally to this work and share first authorship Edited by: Abbas Ghaderi, Shiraz University of Medical Sciences, Iran Reviewed by: Bing Luo, Qingdao University, China; Maria C. Ochoa, University of Navarra, Spain This article was submitted to Cancer Immunity and Immunotherapy, a section of the journal Frontiers in Immunology |
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| Snippet | Tumor-infiltrating lymphocytes (TILs) are considered a manifestation of the host immune response against cancer and tertiary lymphoid structures (TLS) may... BackgroundTumor-infiltrating lymphocytes (TILs) are considered a manifestation of the host immune response against cancer and tertiary lymphoid structures... |
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| SubjectTerms | Carcinoma - diagnosis Carcinoma - immunology Carcinoma - therapy Carcinoma - virology China Decision Support Techniques EBV-associated gastric carcinoma EBV-negative gastric carcinoma Female Herpesvirus 4, Human - immunology Herpesvirus 4, Human - pathogenicity Host-Pathogen Interactions Humans Immunology Lymphocytes, Tumor-Infiltrating - immunology Lymphocytes, Tumor-Infiltrating - virology Male Middle Aged nomogram Nomograms Predictive Value of Tests Prognosis Reproducibility of Results Risk Assessment Risk Factors Stomach Neoplasms - diagnosis Stomach Neoplasms - immunology Stomach Neoplasms - therapy Stomach Neoplasms - virology tertiary lymphoid structures Tertiary Lymphoid Structures - immunology Tertiary Lymphoid Structures - virology Tumor Microenvironment - immunology tumor-infiltrating lymphocytes |
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| Title | Prognostic Value of Tumor-Infiltrating Lymphocytes and Tertiary Lymphoid Structures in Epstein-Barr Virus-Associated and -Negative Gastric Carcinoma |
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