Cargando…

Tumoral Densities of T-Cells and Mast Cells Are Associated With Recurrence in Early-Stage Lung Adenocarcinoma

INTRODUCTION: Lung cancer is the deadliest cancer in the United States and worldwide, and lung adenocarcinoma (LUAD) is the most prevalent histologic subtype in the United States. LUAD exhibits a wide range of aggressiveness and risk of recurrence, but the biological underpinnings of this behavior a...

Descripción completa

Detalles Bibliográficos
Autores principales: Kammer, Michael N., Mori, Hidetoshi, Rowe, Dianna J., Chen, Sheau-Chiann, Vasiukov, Georgii, Atwater, Thomas, Senosain, Maria Fernanda, Antic, Sanja, Zou, Yong, Chen, Heidi, Peikert, Tobias, Deppen, Steve, Grogan, Eric L., Massion, Pierre P., Dubinett, Steve, Lenburg, Marc, Borowsky, Alexander, Maldonado, Fabien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10477685/
https://www.ncbi.nlm.nih.gov/pubmed/37674811
http://dx.doi.org/10.1016/j.jtocrr.2023.100504
_version_ 1785101187497852928
author Kammer, Michael N.
Mori, Hidetoshi
Rowe, Dianna J.
Chen, Sheau-Chiann
Vasiukov, Georgii
Atwater, Thomas
Senosain, Maria Fernanda
Antic, Sanja
Zou, Yong
Chen, Heidi
Peikert, Tobias
Deppen, Steve
Grogan, Eric L.
Massion, Pierre P.
Dubinett, Steve
Lenburg, Marc
Borowsky, Alexander
Maldonado, Fabien
author_facet Kammer, Michael N.
Mori, Hidetoshi
Rowe, Dianna J.
Chen, Sheau-Chiann
Vasiukov, Georgii
Atwater, Thomas
Senosain, Maria Fernanda
Antic, Sanja
Zou, Yong
Chen, Heidi
Peikert, Tobias
Deppen, Steve
Grogan, Eric L.
Massion, Pierre P.
Dubinett, Steve
Lenburg, Marc
Borowsky, Alexander
Maldonado, Fabien
author_sort Kammer, Michael N.
collection PubMed
description INTRODUCTION: Lung cancer is the deadliest cancer in the United States and worldwide, and lung adenocarcinoma (LUAD) is the most prevalent histologic subtype in the United States. LUAD exhibits a wide range of aggressiveness and risk of recurrence, but the biological underpinnings of this behavior are poorly understood. Past studies have focused on the biological characteristics of the tumor itself, but the ability of the immune response to contain tumor growth represents an alternative or complementary hypothesis. Emerging technologies enable us to investigate the spatial distribution of specific cell types within the tumor nest and characterize this immune response. This study aimed to investigate the association between immune cell density within the primary tumor and recurrence-free survival (RFS) in stage I and II LUAD. METHODS: This study is a prospective collection with retrospective evaluation. A total of 100 patients with surgically resected LUAD and at least 5-year follow-ups, including 69 stage I and 31 stages II tumors, were enrolled. Multiplexed immunohistochemistry panels for immune markers were used for measurement. RESULTS: Cox regression models adjusted for sex and EGFR mutation status revealed that the risk of recurrence was reduced by 50% for the unit of one interquartile range (IQR) change in the tumoral T-cell (adjusted hazard ratio per IQR increase = 0.50, 95% confidence interval: 0.27–0.93) and decreased by 64% in mast cell density (adjusted hazard ratio per IQR increase = 0.36, confidence interval: 0.15–0.84). The analyses were reported without the type I error correction for the multiple types of immune cell testing. CONCLUSIONS: Analysis of the density of immune cells within the tumor and surrounding stroma reveals an association between the density of T-cells and RFS and between mast cells and RFS in early-stage LUAD. This preliminary result is a limited study with a small sample size and a lack of an independent validation set.
format Online
Article
Text
id pubmed-10477685
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-104776852023-09-06 Tumoral Densities of T-Cells and Mast Cells Are Associated With Recurrence in Early-Stage Lung Adenocarcinoma Kammer, Michael N. Mori, Hidetoshi Rowe, Dianna J. Chen, Sheau-Chiann Vasiukov, Georgii Atwater, Thomas Senosain, Maria Fernanda Antic, Sanja Zou, Yong Chen, Heidi Peikert, Tobias Deppen, Steve Grogan, Eric L. Massion, Pierre P. Dubinett, Steve Lenburg, Marc Borowsky, Alexander Maldonado, Fabien JTO Clin Res Rep Original Article INTRODUCTION: Lung cancer is the deadliest cancer in the United States and worldwide, and lung adenocarcinoma (LUAD) is the most prevalent histologic subtype in the United States. LUAD exhibits a wide range of aggressiveness and risk of recurrence, but the biological underpinnings of this behavior are poorly understood. Past studies have focused on the biological characteristics of the tumor itself, but the ability of the immune response to contain tumor growth represents an alternative or complementary hypothesis. Emerging technologies enable us to investigate the spatial distribution of specific cell types within the tumor nest and characterize this immune response. This study aimed to investigate the association between immune cell density within the primary tumor and recurrence-free survival (RFS) in stage I and II LUAD. METHODS: This study is a prospective collection with retrospective evaluation. A total of 100 patients with surgically resected LUAD and at least 5-year follow-ups, including 69 stage I and 31 stages II tumors, were enrolled. Multiplexed immunohistochemistry panels for immune markers were used for measurement. RESULTS: Cox regression models adjusted for sex and EGFR mutation status revealed that the risk of recurrence was reduced by 50% for the unit of one interquartile range (IQR) change in the tumoral T-cell (adjusted hazard ratio per IQR increase = 0.50, 95% confidence interval: 0.27–0.93) and decreased by 64% in mast cell density (adjusted hazard ratio per IQR increase = 0.36, confidence interval: 0.15–0.84). The analyses were reported without the type I error correction for the multiple types of immune cell testing. CONCLUSIONS: Analysis of the density of immune cells within the tumor and surrounding stroma reveals an association between the density of T-cells and RFS and between mast cells and RFS in early-stage LUAD. This preliminary result is a limited study with a small sample size and a lack of an independent validation set. Elsevier 2023-03-23 /pmc/articles/PMC10477685/ /pubmed/37674811 http://dx.doi.org/10.1016/j.jtocrr.2023.100504 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Kammer, Michael N.
Mori, Hidetoshi
Rowe, Dianna J.
Chen, Sheau-Chiann
Vasiukov, Georgii
Atwater, Thomas
Senosain, Maria Fernanda
Antic, Sanja
Zou, Yong
Chen, Heidi
Peikert, Tobias
Deppen, Steve
Grogan, Eric L.
Massion, Pierre P.
Dubinett, Steve
Lenburg, Marc
Borowsky, Alexander
Maldonado, Fabien
Tumoral Densities of T-Cells and Mast Cells Are Associated With Recurrence in Early-Stage Lung Adenocarcinoma
title Tumoral Densities of T-Cells and Mast Cells Are Associated With Recurrence in Early-Stage Lung Adenocarcinoma
title_full Tumoral Densities of T-Cells and Mast Cells Are Associated With Recurrence in Early-Stage Lung Adenocarcinoma
title_fullStr Tumoral Densities of T-Cells and Mast Cells Are Associated With Recurrence in Early-Stage Lung Adenocarcinoma
title_full_unstemmed Tumoral Densities of T-Cells and Mast Cells Are Associated With Recurrence in Early-Stage Lung Adenocarcinoma
title_short Tumoral Densities of T-Cells and Mast Cells Are Associated With Recurrence in Early-Stage Lung Adenocarcinoma
title_sort tumoral densities of t-cells and mast cells are associated with recurrence in early-stage lung adenocarcinoma
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10477685/
https://www.ncbi.nlm.nih.gov/pubmed/37674811
http://dx.doi.org/10.1016/j.jtocrr.2023.100504
work_keys_str_mv AT kammermichaeln tumoraldensitiesoftcellsandmastcellsareassociatedwithrecurrenceinearlystagelungadenocarcinoma
AT morihidetoshi tumoraldensitiesoftcellsandmastcellsareassociatedwithrecurrenceinearlystagelungadenocarcinoma
AT rowediannaj tumoraldensitiesoftcellsandmastcellsareassociatedwithrecurrenceinearlystagelungadenocarcinoma
AT chensheauchiann tumoraldensitiesoftcellsandmastcellsareassociatedwithrecurrenceinearlystagelungadenocarcinoma
AT vasiukovgeorgii tumoraldensitiesoftcellsandmastcellsareassociatedwithrecurrenceinearlystagelungadenocarcinoma
AT atwaterthomas tumoraldensitiesoftcellsandmastcellsareassociatedwithrecurrenceinearlystagelungadenocarcinoma
AT senosainmariafernanda tumoraldensitiesoftcellsandmastcellsareassociatedwithrecurrenceinearlystagelungadenocarcinoma
AT anticsanja tumoraldensitiesoftcellsandmastcellsareassociatedwithrecurrenceinearlystagelungadenocarcinoma
AT zouyong tumoraldensitiesoftcellsandmastcellsareassociatedwithrecurrenceinearlystagelungadenocarcinoma
AT chenheidi tumoraldensitiesoftcellsandmastcellsareassociatedwithrecurrenceinearlystagelungadenocarcinoma
AT peikerttobias tumoraldensitiesoftcellsandmastcellsareassociatedwithrecurrenceinearlystagelungadenocarcinoma
AT deppensteve tumoraldensitiesoftcellsandmastcellsareassociatedwithrecurrenceinearlystagelungadenocarcinoma
AT groganericl tumoraldensitiesoftcellsandmastcellsareassociatedwithrecurrenceinearlystagelungadenocarcinoma
AT massionpierrep tumoraldensitiesoftcellsandmastcellsareassociatedwithrecurrenceinearlystagelungadenocarcinoma
AT dubinettsteve tumoraldensitiesoftcellsandmastcellsareassociatedwithrecurrenceinearlystagelungadenocarcinoma
AT lenburgmarc tumoraldensitiesoftcellsandmastcellsareassociatedwithrecurrenceinearlystagelungadenocarcinoma
AT borowskyalexander tumoraldensitiesoftcellsandmastcellsareassociatedwithrecurrenceinearlystagelungadenocarcinoma
AT maldonadofabien tumoraldensitiesoftcellsandmastcellsareassociatedwithrecurrenceinearlystagelungadenocarcinoma