B-Cell Infiltrate in the Tumor Microenvironment Is Associated With Improved Survival in Resected Lung Adenocarcinoma
Introduction: Relapse is common after resection of lung adenocarcinoma (LUAD). Features of the tumor microenvironment (TME) which influence postsurgical survival outcomes are poorly characterized. Here, we analyzed the TME of more than 1500 LUAD specimens to identify the relationship between B-cell...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-07-01
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| Series: | JTO Clinical and Research Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666364323000668 |
| _version_ | 1827893199252750336 |
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| author | Ibiayi Dagogo-Jack, MD Ivan Valiev, MD Nikita Kotlov, MS Anna Belozerova, MD Aleksandra Lopareva, MS, MD Anna Butusova, MS Naira Samarina, PhD Alexandra Boyko, MS Zhongmin Xiang, PhD Monique Johnson, BS Sandrine Degryse, PhD Florence K. Keane, MD Lecia V. Sequist, MD Michael Lanuti, MD Nathan Fowler, MD Mari Mino-Kenudson, MD Alexander Bagaev, PhD |
| author_facet | Ibiayi Dagogo-Jack, MD Ivan Valiev, MD Nikita Kotlov, MS Anna Belozerova, MD Aleksandra Lopareva, MS, MD Anna Butusova, MS Naira Samarina, PhD Alexandra Boyko, MS Zhongmin Xiang, PhD Monique Johnson, BS Sandrine Degryse, PhD Florence K. Keane, MD Lecia V. Sequist, MD Michael Lanuti, MD Nathan Fowler, MD Mari Mino-Kenudson, MD Alexander Bagaev, PhD |
| author_sort | Ibiayi Dagogo-Jack, MD |
| collection | DOAJ |
| description | Introduction: Relapse is common after resection of lung adenocarcinoma (LUAD). Features of the tumor microenvironment (TME) which influence postsurgical survival outcomes are poorly characterized. Here, we analyzed the TME of more than 1500 LUAD specimens to identify the relationship between B-cell infiltration and prognosis. Methods: Whole exome sequencing and bulk RNA sequencing were performed on LUADs and adjacent normal lung tissue. Relapse-free survival and overall survival (OS) were retrospectively correlated with characteristics of the tumor and TME in three data sets. Results: High B-cell content (defined as >10% B cells) was associated with improved OS in both a The Cancer Genome Atlas–resected LUAD data set (p = 0.01) and a separate institutional stage II LUAD data set (p = 0.04, median not reached versus 89.5 mo). A validation cohort consisting of pooled microarray data representing more than 1400 resected stage I to III LUADs confirmed the association between greater B-cell abundance, specifically higher B-cell expression, and longer postsurgical survival (median OS 90 versus 71 mo, p < 0.01). Relapse-free survival was longer for patients with adenocarcinomas with high B-cell content across data sets, but it did not reach statistical significance. Subcategorization of B-cell subsets indicated that high naive B-cell content was most predictive of survival. There was no correlation between programmed death-ligand 1 expression, lymphoid aggregates, or overall immune infiltrate density and survival outcomes across the cohorts. Conclusions: The growing adjuvant immunotherapy repertoire has increased the urgency for identifying prognostic and predictive biomarkers. Comprehensive profiling of more than 1500 LUADs suggests that high tumor-infiltrating B-cell content is a favorable prognostic marker. |
| first_indexed | 2024-03-12T21:50:26Z |
| format | Article |
| id | doaj.art-acbc54d5c39b41eeb5768d2ee56dbc4c |
| institution | Directory Open Access Journal |
| issn | 2666-3643 |
| language | English |
| last_indexed | 2024-03-12T21:50:26Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JTO Clinical and Research Reports |
| spelling | doaj.art-acbc54d5c39b41eeb5768d2ee56dbc4c2023-07-26T04:09:39ZengElsevierJTO Clinical and Research Reports2666-36432023-07-0147100527B-Cell Infiltrate in the Tumor Microenvironment Is Associated With Improved Survival in Resected Lung AdenocarcinomaIbiayi Dagogo-Jack, MD0Ivan Valiev, MD1Nikita Kotlov, MS2Anna Belozerova, MD3Aleksandra Lopareva, MS, MD4Anna Butusova, MS5Naira Samarina, PhD6Alexandra Boyko, MS7Zhongmin Xiang, PhD8Monique Johnson, BS9Sandrine Degryse, PhD10Florence K. Keane, MD11Lecia V. Sequist, MD12Michael Lanuti, MD13Nathan Fowler, MD14Mari Mino-Kenudson, MD15Alexander Bagaev, PhD16Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts; Corresponding author. Address for correspondence: Ibiayi Dagogo-Jack, MD, Department of Thoracic Oncology, Massachusetts General Hospital Cancer Center, 32 Fruit Street, Yawkey 7B Boston, MA 02114.BostonGene Corporation, Waltham, MassachusettsBostonGene Corporation, Waltham, MassachusettsBostonGene Corporation, Waltham, MassachusettsBostonGene Corporation, Waltham, MassachusettsBostonGene Corporation, Waltham, MassachusettsBostonGene Corporation, Waltham, MassachusettsBostonGene Corporation, Waltham, MassachusettsBostonGene Corporation, Waltham, MassachusettsBostonGene Corporation, Waltham, MassachusettsBostonGene Corporation, Waltham, MassachusettsHarvard Medical School, Boston, MassachusettsHarvard Medical School, Boston, MassachusettsHarvard Medical School, Boston, MassachusettsBostonGene Corporation, Waltham, MassachusettsHarvard Medical School, Boston, MassachusettsBostonGene Corporation, Waltham, MassachusettsIntroduction: Relapse is common after resection of lung adenocarcinoma (LUAD). Features of the tumor microenvironment (TME) which influence postsurgical survival outcomes are poorly characterized. Here, we analyzed the TME of more than 1500 LUAD specimens to identify the relationship between B-cell infiltration and prognosis. Methods: Whole exome sequencing and bulk RNA sequencing were performed on LUADs and adjacent normal lung tissue. Relapse-free survival and overall survival (OS) were retrospectively correlated with characteristics of the tumor and TME in three data sets. Results: High B-cell content (defined as >10% B cells) was associated with improved OS in both a The Cancer Genome Atlas–resected LUAD data set (p = 0.01) and a separate institutional stage II LUAD data set (p = 0.04, median not reached versus 89.5 mo). A validation cohort consisting of pooled microarray data representing more than 1400 resected stage I to III LUADs confirmed the association between greater B-cell abundance, specifically higher B-cell expression, and longer postsurgical survival (median OS 90 versus 71 mo, p < 0.01). Relapse-free survival was longer for patients with adenocarcinomas with high B-cell content across data sets, but it did not reach statistical significance. Subcategorization of B-cell subsets indicated that high naive B-cell content was most predictive of survival. There was no correlation between programmed death-ligand 1 expression, lymphoid aggregates, or overall immune infiltrate density and survival outcomes across the cohorts. Conclusions: The growing adjuvant immunotherapy repertoire has increased the urgency for identifying prognostic and predictive biomarkers. Comprehensive profiling of more than 1500 LUADs suggests that high tumor-infiltrating B-cell content is a favorable prognostic marker.http://www.sciencedirect.com/science/article/pii/S2666364323000668B cellsresectedlung cancertumor microenvironment |
| spellingShingle | Ibiayi Dagogo-Jack, MD Ivan Valiev, MD Nikita Kotlov, MS Anna Belozerova, MD Aleksandra Lopareva, MS, MD Anna Butusova, MS Naira Samarina, PhD Alexandra Boyko, MS Zhongmin Xiang, PhD Monique Johnson, BS Sandrine Degryse, PhD Florence K. Keane, MD Lecia V. Sequist, MD Michael Lanuti, MD Nathan Fowler, MD Mari Mino-Kenudson, MD Alexander Bagaev, PhD B-Cell Infiltrate in the Tumor Microenvironment Is Associated With Improved Survival in Resected Lung Adenocarcinoma JTO Clinical and Research Reports B cells resected lung cancer tumor microenvironment |
| title | B-Cell Infiltrate in the Tumor Microenvironment Is Associated With Improved Survival in Resected Lung Adenocarcinoma |
| title_full | B-Cell Infiltrate in the Tumor Microenvironment Is Associated With Improved Survival in Resected Lung Adenocarcinoma |
| title_fullStr | B-Cell Infiltrate in the Tumor Microenvironment Is Associated With Improved Survival in Resected Lung Adenocarcinoma |
| title_full_unstemmed | B-Cell Infiltrate in the Tumor Microenvironment Is Associated With Improved Survival in Resected Lung Adenocarcinoma |
| title_short | B-Cell Infiltrate in the Tumor Microenvironment Is Associated With Improved Survival in Resected Lung Adenocarcinoma |
| title_sort | b cell infiltrate in the tumor microenvironment is associated with improved survival in resected lung adenocarcinoma |
| topic | B cells resected lung cancer tumor microenvironment |
| url | http://www.sciencedirect.com/science/article/pii/S2666364323000668 |
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