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CSF1R-Expressing Tumor-Associated Macrophages, Smoking and Survival in Lung Adenocarcinoma: Analyses Using Quantitative Phosphor-Integrated Dot Staining

CSF1R-expressing tumor-associated macrophages (TAMs) induce a tumor-promoting microenvironment by regulating immunity. Evidence demonstrates that the expression and single nucleotide polymorphisms of CSF1R relate with survival and risk of lung cancer in never smokers. However, no previous studies ha...

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Autores principales: Inamura, Kentaro, Shigematsu, Yasuyuki, Ninomiya, Hironori, Nakashima, Yasuhiro, Kobayashi, Maki, Saito, Haruyuki, Takahashi, Katsuhiro, Futaya, Etsuko, Okumura, Sakae, Ishikawa, Yuichi, Kanda, Hiroaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115958/
https://www.ncbi.nlm.nih.gov/pubmed/30065206
http://dx.doi.org/10.3390/cancers10080252
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author Inamura, Kentaro
Shigematsu, Yasuyuki
Ninomiya, Hironori
Nakashima, Yasuhiro
Kobayashi, Maki
Saito, Haruyuki
Takahashi, Katsuhiro
Futaya, Etsuko
Okumura, Sakae
Ishikawa, Yuichi
Kanda, Hiroaki
author_facet Inamura, Kentaro
Shigematsu, Yasuyuki
Ninomiya, Hironori
Nakashima, Yasuhiro
Kobayashi, Maki
Saito, Haruyuki
Takahashi, Katsuhiro
Futaya, Etsuko
Okumura, Sakae
Ishikawa, Yuichi
Kanda, Hiroaki
author_sort Inamura, Kentaro
collection PubMed
description CSF1R-expressing tumor-associated macrophages (TAMs) induce a tumor-promoting microenvironment by regulating immunity. Evidence demonstrates that the expression and single nucleotide polymorphisms of CSF1R relate with survival and risk of lung cancer in never smokers. However, no previous studies have examined the association of CSF1R expression in TAMs with mortality or whether the prognostic association differs according to smoking status in lung adenocarcinoma. Quantitative phosphor-integrated dot staining was used to precisely assess CSF1R expression in TAMs. Using 195 consecutive cases of lung adenocarcinoma, we examined the association of CSF1R expression with mortality and whether the prognostic association differs according to smoking status. We observed high expression levels of CSF1R in TAMs in 65 of 195 (33%) cases of lung adenocarcinoma. High expression levels of CSF1R were associated with high lung cancer-specific mortality (log-rank p = 0.037; hazard ratio (HR) = 1.61, 95% confidence interval (CI) = 1.02−2.52, p = 0.043). This prognostic association differed according to smoking status (p for interaction = 0.049, between never-smoking and ever-smoking patients). The association between high expression levels of CSF1R and lung cancer-specific mortality was stronger in never-smoking patients (log-rank p = 0.0027; HR = 2.90, 95% CI = 1.41−6.11, p = 0.0041) than in ever-smoking patients (log-rank p = 0.73; HR = 1.11, 95% CI = 0.59−2.00, p = 0.73). The findings suggest that CSF1R-expressing TAMs may exert stronger tumor-promoting immunity in never-smoking patients with lung adenocarcinoma and serve as a therapeutic target in precision immunotherapies.
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spelling pubmed-61159582018-08-31 CSF1R-Expressing Tumor-Associated Macrophages, Smoking and Survival in Lung Adenocarcinoma: Analyses Using Quantitative Phosphor-Integrated Dot Staining Inamura, Kentaro Shigematsu, Yasuyuki Ninomiya, Hironori Nakashima, Yasuhiro Kobayashi, Maki Saito, Haruyuki Takahashi, Katsuhiro Futaya, Etsuko Okumura, Sakae Ishikawa, Yuichi Kanda, Hiroaki Cancers (Basel) Article CSF1R-expressing tumor-associated macrophages (TAMs) induce a tumor-promoting microenvironment by regulating immunity. Evidence demonstrates that the expression and single nucleotide polymorphisms of CSF1R relate with survival and risk of lung cancer in never smokers. However, no previous studies have examined the association of CSF1R expression in TAMs with mortality or whether the prognostic association differs according to smoking status in lung adenocarcinoma. Quantitative phosphor-integrated dot staining was used to precisely assess CSF1R expression in TAMs. Using 195 consecutive cases of lung adenocarcinoma, we examined the association of CSF1R expression with mortality and whether the prognostic association differs according to smoking status. We observed high expression levels of CSF1R in TAMs in 65 of 195 (33%) cases of lung adenocarcinoma. High expression levels of CSF1R were associated with high lung cancer-specific mortality (log-rank p = 0.037; hazard ratio (HR) = 1.61, 95% confidence interval (CI) = 1.02−2.52, p = 0.043). This prognostic association differed according to smoking status (p for interaction = 0.049, between never-smoking and ever-smoking patients). The association between high expression levels of CSF1R and lung cancer-specific mortality was stronger in never-smoking patients (log-rank p = 0.0027; HR = 2.90, 95% CI = 1.41−6.11, p = 0.0041) than in ever-smoking patients (log-rank p = 0.73; HR = 1.11, 95% CI = 0.59−2.00, p = 0.73). The findings suggest that CSF1R-expressing TAMs may exert stronger tumor-promoting immunity in never-smoking patients with lung adenocarcinoma and serve as a therapeutic target in precision immunotherapies. MDPI 2018-07-31 /pmc/articles/PMC6115958/ /pubmed/30065206 http://dx.doi.org/10.3390/cancers10080252 Text en © 2018 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Inamura, Kentaro
Shigematsu, Yasuyuki
Ninomiya, Hironori
Nakashima, Yasuhiro
Kobayashi, Maki
Saito, Haruyuki
Takahashi, Katsuhiro
Futaya, Etsuko
Okumura, Sakae
Ishikawa, Yuichi
Kanda, Hiroaki
CSF1R-Expressing Tumor-Associated Macrophages, Smoking and Survival in Lung Adenocarcinoma: Analyses Using Quantitative Phosphor-Integrated Dot Staining
title CSF1R-Expressing Tumor-Associated Macrophages, Smoking and Survival in Lung Adenocarcinoma: Analyses Using Quantitative Phosphor-Integrated Dot Staining
title_full CSF1R-Expressing Tumor-Associated Macrophages, Smoking and Survival in Lung Adenocarcinoma: Analyses Using Quantitative Phosphor-Integrated Dot Staining
title_fullStr CSF1R-Expressing Tumor-Associated Macrophages, Smoking and Survival in Lung Adenocarcinoma: Analyses Using Quantitative Phosphor-Integrated Dot Staining
title_full_unstemmed CSF1R-Expressing Tumor-Associated Macrophages, Smoking and Survival in Lung Adenocarcinoma: Analyses Using Quantitative Phosphor-Integrated Dot Staining
title_short CSF1R-Expressing Tumor-Associated Macrophages, Smoking and Survival in Lung Adenocarcinoma: Analyses Using Quantitative Phosphor-Integrated Dot Staining
title_sort csf1r-expressing tumor-associated macrophages, smoking and survival in lung adenocarcinoma: analyses using quantitative phosphor-integrated dot staining
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115958/
https://www.ncbi.nlm.nih.gov/pubmed/30065206
http://dx.doi.org/10.3390/cancers10080252
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