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Spatial heterogeneity of T cell repertoire across NSCLC tumors, tumor edges, adjacent and distant lung tissues

BACKGROUND: A better understanding of T cells in lung cancer and their distribution across tumor-adjacent lungs and peripheral blood is needed to improve efficacy and minimize toxicity from immunotherapy to lung cancer patients. METHODS: Here, we performed CDR3β TCR sequencing of 136 samples from 20...

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Autores principales: Hu, Qikang, Frank, Meredith L., Gao, Yang, Ji, Liyan, Peng, Muyun, Chen, Chen, Wang, Bin, Hu, Yan, Wu, Zeyu, Li, Jina, Shu, Lu, He, Qiongzhi, Zhang, Yingqian, Xia, Xuefeng, Zhang, Jianjun, Yi, Xin, Reuben, Alexandre, Yu, Fenglei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10591778/
https://www.ncbi.nlm.nih.gov/pubmed/37876834
http://dx.doi.org/10.1080/2162402X.2023.2233399
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author Hu, Qikang
Frank, Meredith L.
Gao, Yang
Ji, Liyan
Peng, Muyun
Chen, Chen
Wang, Bin
Hu, Yan
Wu, Zeyu
Li, Jina
Shu, Lu
He, Qiongzhi
Zhang, Yingqian
Xia, Xuefeng
Zhang, Jianjun
Yi, Xin
Reuben, Alexandre
Yu, Fenglei
author_facet Hu, Qikang
Frank, Meredith L.
Gao, Yang
Ji, Liyan
Peng, Muyun
Chen, Chen
Wang, Bin
Hu, Yan
Wu, Zeyu
Li, Jina
Shu, Lu
He, Qiongzhi
Zhang, Yingqian
Xia, Xuefeng
Zhang, Jianjun
Yi, Xin
Reuben, Alexandre
Yu, Fenglei
author_sort Hu, Qikang
collection PubMed
description BACKGROUND: A better understanding of T cells in lung cancer and their distribution across tumor-adjacent lungs and peripheral blood is needed to improve efficacy and minimize toxicity from immunotherapy to lung cancer patients. METHODS: Here, we performed CDR3β TCR sequencing of 136 samples from 20 patients with early-stage NSCLC including peripheral blood mononuclear cells, tumors, tumor edges (<1 cm from tumor), as well as adjacent lungs 1 cm, 2 cm, 5 cm, and 10 cm away from the tumor to gain insight into the spatial heterogeneity of T cells across the lungs in patients with NSCLC. PD-L1, CD4, and CD8 expression was assessed using immunohistochemical staining, and genomic features were derived by targeted sequencing of 1,021 cancer-related genes. Multiplex immunohistochemistry against PD-1, CTLA4, LAG3, and TIM3 was performed on four patients to assess T cell exhaustion. RESULTS: Our study reveals a decreasing gradient in TIL Tumor Infiltrating Lymphocytes homology with tumor edge, adjacent lungs, and peripheral blood but no discernible distance-associated patterns of T cell trafficking within the adjacent lung itself. Furthermore, we show a decrease in pathogen-specific TCRs in regions with high T cell clonality and PD-L1 expression. CONCLUSIONS: Exclusion in T exhaustion cells at play across the lungs of patients with NSCLC may potentially be the mechanism for lung cancer occurrence.
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spelling pubmed-105917782023-10-24 Spatial heterogeneity of T cell repertoire across NSCLC tumors, tumor edges, adjacent and distant lung tissues Hu, Qikang Frank, Meredith L. Gao, Yang Ji, Liyan Peng, Muyun Chen, Chen Wang, Bin Hu, Yan Wu, Zeyu Li, Jina Shu, Lu He, Qiongzhi Zhang, Yingqian Xia, Xuefeng Zhang, Jianjun Yi, Xin Reuben, Alexandre Yu, Fenglei Oncoimmunology Original Research BACKGROUND: A better understanding of T cells in lung cancer and their distribution across tumor-adjacent lungs and peripheral blood is needed to improve efficacy and minimize toxicity from immunotherapy to lung cancer patients. METHODS: Here, we performed CDR3β TCR sequencing of 136 samples from 20 patients with early-stage NSCLC including peripheral blood mononuclear cells, tumors, tumor edges (<1 cm from tumor), as well as adjacent lungs 1 cm, 2 cm, 5 cm, and 10 cm away from the tumor to gain insight into the spatial heterogeneity of T cells across the lungs in patients with NSCLC. PD-L1, CD4, and CD8 expression was assessed using immunohistochemical staining, and genomic features were derived by targeted sequencing of 1,021 cancer-related genes. Multiplex immunohistochemistry against PD-1, CTLA4, LAG3, and TIM3 was performed on four patients to assess T cell exhaustion. RESULTS: Our study reveals a decreasing gradient in TIL Tumor Infiltrating Lymphocytes homology with tumor edge, adjacent lungs, and peripheral blood but no discernible distance-associated patterns of T cell trafficking within the adjacent lung itself. Furthermore, we show a decrease in pathogen-specific TCRs in regions with high T cell clonality and PD-L1 expression. CONCLUSIONS: Exclusion in T exhaustion cells at play across the lungs of patients with NSCLC may potentially be the mechanism for lung cancer occurrence. Taylor & Francis 2023-10-20 /pmc/articles/PMC10591778/ /pubmed/37876834 http://dx.doi.org/10.1080/2162402X.2023.2233399 Text en © 2023 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
spellingShingle Original Research
Hu, Qikang
Frank, Meredith L.
Gao, Yang
Ji, Liyan
Peng, Muyun
Chen, Chen
Wang, Bin
Hu, Yan
Wu, Zeyu
Li, Jina
Shu, Lu
He, Qiongzhi
Zhang, Yingqian
Xia, Xuefeng
Zhang, Jianjun
Yi, Xin
Reuben, Alexandre
Yu, Fenglei
Spatial heterogeneity of T cell repertoire across NSCLC tumors, tumor edges, adjacent and distant lung tissues
title Spatial heterogeneity of T cell repertoire across NSCLC tumors, tumor edges, adjacent and distant lung tissues
title_full Spatial heterogeneity of T cell repertoire across NSCLC tumors, tumor edges, adjacent and distant lung tissues
title_fullStr Spatial heterogeneity of T cell repertoire across NSCLC tumors, tumor edges, adjacent and distant lung tissues
title_full_unstemmed Spatial heterogeneity of T cell repertoire across NSCLC tumors, tumor edges, adjacent and distant lung tissues
title_short Spatial heterogeneity of T cell repertoire across NSCLC tumors, tumor edges, adjacent and distant lung tissues
title_sort spatial heterogeneity of t cell repertoire across nsclc tumors, tumor edges, adjacent and distant lung tissues
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10591778/
https://www.ncbi.nlm.nih.gov/pubmed/37876834
http://dx.doi.org/10.1080/2162402X.2023.2233399
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