期刊
GASTRIC CANCER
卷 21, 期 1, 页码 31-40出版社
SPRINGER
DOI: 10.1007/s10120-017-0760-3
关键词
Gastric adenocarcinoma; Programmed death protein 1; Tumor microenvironment; Macrophages
资金
- Schecter Private Foundation
- Rivercreek Foundation
- Kevin Fund
- Myer Fund
- Dio Fund
- Milrod Fund
- University of Texas MD Anderson Cancer Center (Houston, TX, USA)
- National Cancer Institute
- Department of Defense awards [CA138671, CA172741, CA129926, CA150334, CA160433]
- Program for Advancing Strategic International Networks to Accelerate the Circulation of Talented Researchers from Japan Society for the Promotion of Science
- Caporella family
- Dallas family
- Sultan family
- Park family
- Smith family
- Frazier family
- Oaks family
- Vanstekelenberg family
- Planjery family
- Cantu family
- NATIONAL CANCER INSTITUTE [R01CA172741] Funding Source: NIH RePORTER
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.
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