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- Title
Tumor-associated macrophage infiltration is highly associated with PD-L1 expression in gastric adenocarcinoma.
- Authors
Harada, Kazuto; Dong, Xiaochuan; Estrella, Jeannelyn S.; Correa, Arlene M.; Xu, Yan; Hofstetter, Wayne L.; Sudo, Kazuki; Onodera, Hisashi; Suzuki, Koyu; Suzuki, Akihiro; Johnson, Randy L.; Wang, Zhenning; Song, Shumei; Ajani, Jaffer A.
- Abstract
Background: 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. Methods: 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. Results: 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). Conclusion: 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.
- Subjects
LIGANDS (Biochemistry); IMMUNOSUPPRESSION; ADENOCARCINOMA; MACROPHAGES; CANCER cells; LOGISTIC regression analysis; THERAPEUTICS
- Publication
Gastric Cancer, 2018, Vol 21, Issue 1, p31
- ISSN
1436-3291
- Publication type
Article
- DOI
10.1007/s10120-017-0760-3