Stromal PD-1+ tumor-associated macrophages predict poor prognosis in lung adenocarcinoma.
Hum Pathol
; 97: 68-79, 2020 03.
Article
em En
| MEDLINE
| ID: mdl-31926212
ABSTRACT
Immunotherapies targeting programmed cell death protein 1 (PD-1)/PD-1 ligand (PD-L1) axis have been emerging as a promising therapeutic strategy to treat lung cancer. PD-1 is preferentially expressed by activated T lymphocytes; but whether/how its expression by tumor-associated macrophages (TAMs) in lung adenocarcinoma remains elusive. Herein, we investigate the frequency of PD-1 expression on TAMs in mouse allografts by flow cytometry analysis and evaluate the spatial distribution and clinicopathological significance of PD-1+ TAMs in 213 cases of human lung adenocarcinoma specimens by immunohistochemical staining. We find the expression of PD-1 by both mouse and human TAMs. Mouse PD-1+ TAMs possess unique transcriptional profile as compared to PD-1- TAMs. Furthermore, PD-1 is preferentially expressed by CD163+ TAMs in the tumor stroma than those in the tumor islets of lung adenocarcinoma. Stromal PD-1+ TAM infiltration is an independent predictor of reduced survival as determined by univariate (P < .001) and multivariate (P = .023) analysis. Moreover, patients with high stromal PD-1+ TAMs but low tumor cell PD-L1 expression have the shortest survival (P = .0001). Our study demonstrates that PD-1+ TAMs have unique gene expression characteristics and PD-1+ TAMs in the tumor stroma is a potential prognostic factor in lung adenocarcinoma, suggesting that a better understanding of PD-1+ TAMs will be beneficial for immunotherapy of lung adenocarcinoma patients.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article