Title |
Tumor-associated macrophage infiltration is highly associated with PD-L1 expression in gastric adenocarcinoma
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Published in |
Gastric Cancer, August 2017
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DOI | 10.1007/s10120-017-0760-3 |
Pubmed ID | |
Authors |
Kazuto Harada, Xiaochuan Dong, Jeannelyn S. Estrella, Arlene M. Correa, Yan Xu, Wayne L. Hofstetter, Kazuki Sudo, Hisashi Onodera, Koyu Suzuki, Akihiro Suzuki, Randy L. Johnson, Zhenning Wang, Shumei Song, Jaffer A. Ajani |
Abstract |
Programmed death ligand 1 (PD-L1) is a key protein upregulated by tumor cells to suppress immune responses. Tumor-associated macrophages (TAMs) play a major role in this immunosuppression, but the relationship between PD-L1 expression and TAMs remains unclear in gastric adenocarcinoma (GAC). We simultaneously examined expression of PD-L1 and TAMs in GAC. We performed immunohistochemical staining for PD-L1, CD68 (pan-macrophage), and CD163 (M2-like macrophage) in 217 GAC samples using a tissue microarray. Expression of PD-L1 and CD68- and CD163-positive cells was evaluated using the Cytoplasmic V2.0 algorithm in Aperio ImageScope software, and logistic regression analysis was used to compare expression patterns between groups. Thirty-one samples (14%) were positive for PD-L1 expression. The mean (± standard error) rates of infiltration were 6.83 ± 0.38% for CD68-positive cells and 6.16 ± 0.29% for CD163-positive cells. The mean rate of CD163-positive cell infiltration was significantly higher in diffuse GAC than in intestinal GAC (diffuse n = 111, 6.91%; intestinal n = 91, 5.26%; p = 0.006), but the mean rate of CD68-positive cell infiltration was similar between these types (p = 0.38). The mean infiltration rates of CD68- and CD163-positive cells in PD-L1-positive GAC were significantly higher than in PD-L1-negative GAC (CD68 p = 0.0002; CD163 p < 0.0001). In multivariate logistic regression analyses, CD163-positive cell infiltration was associated with PD-L1 expression (odds ratio 1.13; 95% confidence interval 1.02-1.25; p = 0.021). M2-like macrophage infiltration is highly associated with PD-L1 expression in GAC cells, suggesting that macrophage infiltration can serve as a potential therapeutic target. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Denmark | 1 | 33% |
Spain | 1 | 33% |
Unknown | 1 | 33% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 67% |
Practitioners (doctors, other healthcare professionals) | 1 | 33% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 43 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 6 | 14% |
Researcher | 6 | 14% |
Student > Master | 6 | 14% |
Professor > Associate Professor | 4 | 9% |
Student > Doctoral Student | 3 | 7% |
Other | 8 | 19% |
Unknown | 10 | 23% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 17 | 40% |
Biochemistry, Genetics and Molecular Biology | 8 | 19% |
Agricultural and Biological Sciences | 2 | 5% |
Nursing and Health Professions | 1 | 2% |
Immunology and Microbiology | 1 | 2% |
Other | 1 | 2% |
Unknown | 13 | 30% |