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Clinical Implications and Molecular Characterization of Drebrin-Positive, Tumor-Infiltrating Exhausted T Cells in Lung Cancer

T cells express an actin-binding protein, drebrin, which is recruited to the contact site between the T cells and antigen-presenting cells during the formation of immunological synapses. However, little is known about the clinical implications of drebrin-expressing, tumor-infiltrating lymphocytes (T...

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Autores principales: Imamura, Kosuke, Tomita, Yusuke, Sato, Ryo, Ikeda, Tokunori, Iyama, Shinji, Jodai, Takayuki, Takahashi, Misako, Takaki, Akira, Akaike, Kimitaka, Hamada, Shohei, Sakata, Shinya, Saruwatari, Koichi, Saeki, Sho, Ikeda, Koei, Suzuki, Makoto, Sakagami, Takuro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9694580/
https://www.ncbi.nlm.nih.gov/pubmed/36430217
http://dx.doi.org/10.3390/ijms232213723
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author Imamura, Kosuke
Tomita, Yusuke
Sato, Ryo
Ikeda, Tokunori
Iyama, Shinji
Jodai, Takayuki
Takahashi, Misako
Takaki, Akira
Akaike, Kimitaka
Hamada, Shohei
Sakata, Shinya
Saruwatari, Koichi
Saeki, Sho
Ikeda, Koei
Suzuki, Makoto
Sakagami, Takuro
author_facet Imamura, Kosuke
Tomita, Yusuke
Sato, Ryo
Ikeda, Tokunori
Iyama, Shinji
Jodai, Takayuki
Takahashi, Misako
Takaki, Akira
Akaike, Kimitaka
Hamada, Shohei
Sakata, Shinya
Saruwatari, Koichi
Saeki, Sho
Ikeda, Koei
Suzuki, Makoto
Sakagami, Takuro
author_sort Imamura, Kosuke
collection PubMed
description T cells express an actin-binding protein, drebrin, which is recruited to the contact site between the T cells and antigen-presenting cells during the formation of immunological synapses. However, little is known about the clinical implications of drebrin-expressing, tumor-infiltrating lymphocytes (TILs). To address this issue, we evaluated 34 surgical specimens of pathological stage I–IIIA squamous cell lung cancer. The immune context of primary tumors was investigated using fluorescent multiplex immunohistochemistry. The high-speed scanning of whole-slide images was performed, and the tissue localization of TILs in the tumor cell nest and surrounding stroma was automatically profiled and quantified. Drebrin-expressing T cells were characterized using drebrin(+) T cells induced in vitro and publicly available single-cell RNA sequence (scRNA-seq) database. Survival analysis using the propensity scores revealed that a high infiltration of drebrin(+) TILs within the tumor cell nest was independently associated with short relapse-free survival and overall survival. Drebrin(+) T cells induced in vitro co-expressed multiple exhaustion-associated molecules. The scRNA-seq analyses confirmed that the exhausted tumor-infiltrating CD8(+) T cells specifically expressed drebrin. Our study suggests that drebrin-expressing T cells present an exhausted phenotype and that tumor-infiltrating drebrin(+) T cells affect clinical outcomes in patients with resectable squamous cell lung cancer.
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spelling pubmed-96945802022-11-26 Clinical Implications and Molecular Characterization of Drebrin-Positive, Tumor-Infiltrating Exhausted T Cells in Lung Cancer Imamura, Kosuke Tomita, Yusuke Sato, Ryo Ikeda, Tokunori Iyama, Shinji Jodai, Takayuki Takahashi, Misako Takaki, Akira Akaike, Kimitaka Hamada, Shohei Sakata, Shinya Saruwatari, Koichi Saeki, Sho Ikeda, Koei Suzuki, Makoto Sakagami, Takuro Int J Mol Sci Article T cells express an actin-binding protein, drebrin, which is recruited to the contact site between the T cells and antigen-presenting cells during the formation of immunological synapses. However, little is known about the clinical implications of drebrin-expressing, tumor-infiltrating lymphocytes (TILs). To address this issue, we evaluated 34 surgical specimens of pathological stage I–IIIA squamous cell lung cancer. The immune context of primary tumors was investigated using fluorescent multiplex immunohistochemistry. The high-speed scanning of whole-slide images was performed, and the tissue localization of TILs in the tumor cell nest and surrounding stroma was automatically profiled and quantified. Drebrin-expressing T cells were characterized using drebrin(+) T cells induced in vitro and publicly available single-cell RNA sequence (scRNA-seq) database. Survival analysis using the propensity scores revealed that a high infiltration of drebrin(+) TILs within the tumor cell nest was independently associated with short relapse-free survival and overall survival. Drebrin(+) T cells induced in vitro co-expressed multiple exhaustion-associated molecules. The scRNA-seq analyses confirmed that the exhausted tumor-infiltrating CD8(+) T cells specifically expressed drebrin. Our study suggests that drebrin-expressing T cells present an exhausted phenotype and that tumor-infiltrating drebrin(+) T cells affect clinical outcomes in patients with resectable squamous cell lung cancer. MDPI 2022-11-08 /pmc/articles/PMC9694580/ /pubmed/36430217 http://dx.doi.org/10.3390/ijms232213723 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Imamura, Kosuke
Tomita, Yusuke
Sato, Ryo
Ikeda, Tokunori
Iyama, Shinji
Jodai, Takayuki
Takahashi, Misako
Takaki, Akira
Akaike, Kimitaka
Hamada, Shohei
Sakata, Shinya
Saruwatari, Koichi
Saeki, Sho
Ikeda, Koei
Suzuki, Makoto
Sakagami, Takuro
Clinical Implications and Molecular Characterization of Drebrin-Positive, Tumor-Infiltrating Exhausted T Cells in Lung Cancer
title Clinical Implications and Molecular Characterization of Drebrin-Positive, Tumor-Infiltrating Exhausted T Cells in Lung Cancer
title_full Clinical Implications and Molecular Characterization of Drebrin-Positive, Tumor-Infiltrating Exhausted T Cells in Lung Cancer
title_fullStr Clinical Implications and Molecular Characterization of Drebrin-Positive, Tumor-Infiltrating Exhausted T Cells in Lung Cancer
title_full_unstemmed Clinical Implications and Molecular Characterization of Drebrin-Positive, Tumor-Infiltrating Exhausted T Cells in Lung Cancer
title_short Clinical Implications and Molecular Characterization of Drebrin-Positive, Tumor-Infiltrating Exhausted T Cells in Lung Cancer
title_sort clinical implications and molecular characterization of drebrin-positive, tumor-infiltrating exhausted t cells in lung cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9694580/
https://www.ncbi.nlm.nih.gov/pubmed/36430217
http://dx.doi.org/10.3390/ijms232213723
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