Dataset Information

High CCR4 expression in the tumor microenvironment is a poor prognostic indicator in lung adenocarcinoma.

ABSTRACT:

Background

Clinical trials of anti-CCR4 antibody for solid cancers with or without other immune-modulating agents including immune checkpoint blockade therapy are currently underway. However, little is known about the roles of CCR4⁺ lymphocytes and their prognostic impact in lung cancer. We hypothesized that high CCR4 expression in the tumor microenvironment would be associated with a poor prognosis and would act as a biomarker in lung adenocarcinoma.

Methods

First, the prognostic impact of CCR4 gene expression was explored using pooled data from public transcriptomic databases with online survival analysis software. Second, tissue microarrays (TMAs) were constructed from resected lung adenocarcinoma specimens from tumors up to 3 cm in size. The density of CCR4⁺ lymphocytes infiltrating the tumor was then assessed by immunohistochemistry and related to survival. Confounding factors were controlled for by multivariate analysis using the Cox proportional hazards model.

Results

Higher than median expression of the CCR4 gene was identified as an independent poor prognostic factor for overall survival (OS) by multivariate analysis of 720 lung adenocarcinoma patients in the public databases [HR =1.55 (95% CI: 1.03-2.35), P=0.037]. Consistent with this, high CCR4⁺ tumor-infiltrating lymphocyte (TIL) density was found to be an independent poor prognostic factor for both OS [HR =2.24 (1.01-5.34), P=0.049] and recurrence-free survival (RFS) [HR =2.20 (1.16-4.39), P=0.017] in the patients from whom TMA were obtained (n=180). Age, male gender, predominantly non-lepidic histological subtype, nodal involvement, and low CD8⁺ TIL density were also independent poor prognostic factors. However, FOXP3 gene expression and Foxp3⁺ lymphocyte infiltration did not possess any prognostic value in either study.

Conclusions

High CCR4 expression in the tumor microenvironment may be a poor prognostic factor in lung adenocarcinoma. Patients with high CCR4⁺ lymphocyte infiltration may have a poor prognosis and thus be suitable candidates for clinical trials of anti-CCR4 antibody treatment.

SUBMITTER: Karasaki T

PROVIDER: S-EPMC6129889 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Publications

High CCR4 expression in the tumor microenvironment is a poor prognostic indicator in lung adenocarcinoma.

Karasaki Takahiro T Qiang Guangliang G Anraku Masaki M Sun Yanbin Y Shinozaki-Ushiku Aya A Sato Eiichi E Kashiwabara Kosuke K Nagayama Kazuhiro K Nitadori Jun-Ichi JI Sato Masaaki M Murakawa Tomohiro T Kakimi Kazuhiro K Fukayama Masashi M Nakajima Jun J

Journal of thoracic disease 20180801 8

<h4>Background</h4>Clinical trials of anti-CCR4 antibody for solid cancers with or without other immune-modulating agents including immune checkpoint blockade therapy are currently underway. However, little is known about the roles of CCR4<sup>+</sup> lymphocytes and their prognostic impact in lung cancer. We hypothesized that high CCR4 expression in the tumor microenvironment would be associated with a poor prognosis and would act as a biomarker in lung adenocarcinoma.<h4>Methods</h4>First, the ...[more]

PMID: 30233846

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Dataset Information

High CCR4 expression in the tumor microenvironment is a poor prognostic indicator in lung adenocarcinoma.

Background

Methods

Results

Conclusions

Publications

High CCR4 expression in the tumor microenvironment is a poor prognostic indicator in lung adenocarcinoma.

Similar Datasets

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