肿瘤相关的CD163 M2巨噬细胞浸润与宫颈癌中PD-L1表达高度相关。
Tumor-Associated CD163 M2 Macrophage Infiltration is Highly Associated with PD-L1 Expression in Cervical Cancer.
作者信息
Guo Fan, Feng Yang-Chun, Zhao Gang, Zhang Ran, Cheng Zhen-Zhen, Kong Wei-Na, Wu Hui-Li, Xu Bin, Lv Xiang, Ma Xiu-Min
机构信息
State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Laboratory Center, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi 830011, People's Republic of China.
The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, People's Republic of China.
出版信息
Cancer Manag Res. 2020 Jul 15;12:5831-5843. doi: 10.2147/CMAR.S257692. eCollection 2020.
BACKGROUND
Programmed death-ligand 1 (PD-L1) is a negative costimulatory molecule, and its main function is widely considered to be in the regulation of T cells. Tumor-associated macrophages (TAMs) are an important part of the tumor microenvironment, and they also play an important role in immunosuppression. However, the relationship between the expression of PD-L1 and TAMs in cervical carcinoma (CC) remains unclear. We detected the expression of PD-L1 and TAMs in tumor tissue to study the correlation between them.
METHODS
Immunohistochemical staining of PD-L1, CD68 (pan-macrophage), and CD163 (M2-like macrophage) was performed in 120 cases of cervical squamous cell carcinoma. Logistic regression analysis was used to evaluate the predictors related to positive PD-L1 expression. We also apply the Kaplan-Meier method to study the recurrence-free and overall survival rate of CC patients.
RESULTS
The increase in PD-L1 expression in tumor cells (TC) was significantly correlated with the increase in CD163 density (=0.8550, <0.0001), while PD-L1 in the stroma was also significantly associated with the intratumoral density of CD68- or CD163-positive cells (CD68 <0.0001; CD163 =0.0009). The mean infiltration rates of CD68- and CD163-positive cells in PD-L1-positive TC were significantly higher than in PD-L1-negative TC (CD68 p=0.0095; CD163 <0.0001). In multivariate logistic regression analyses, only the density of CD163-positive cells was correlated with the expression of PD-L1 in TC cells (OR 1.52; =0.032). In prognostic analysis, PD-L1 more than 10% was significantly correlated with short RFS (HR=2.66; =0.028). For CD163 macrophage evaluation, the density above the median was also significantly correlated with RFS (HR=2.48; =0.021).
CONCLUSION
CD163 M2-like macrophage infiltration is highly associated with PD-L1 expression in CC, suggesting that macrophage infiltration can serve as a potential therapeutic target.
背景
程序性死亡配体1（PD-L1）是一种负性共刺激分子，其主要功能被广泛认为是调节T细胞。肿瘤相关巨噬细胞（TAM）是肿瘤微环境的重要组成部分，它们在免疫抑制中也发挥着重要作用。然而，宫颈癌（CC）中PD-L1表达与TAM之间的关系仍不清楚。我们检测了肿瘤组织中PD-L1和TAM的表达，以研究它们之间的相关性。
方法
对120例宫颈鳞状细胞癌进行PD-L1、CD68（全巨噬细胞）和CD163（M2样巨噬细胞）的免疫组织化学染色。采用逻辑回归分析评估与PD-L1阳性表达相关的预测因素。我们还应用Kaplan-Meier方法研究CC患者的无复发生存率和总生存率。
结果
肿瘤细胞（TC）中PD-L1表达的增加与CD163密度的增加显著相关（=0.8550，<0.0001），而基质中的PD-L1也与CD68或CD163阳性细胞的瘤内密度显著相关（CD68<0.0001；CD163=0.0009）。PD-L1阳性TC中CD68和CD163阳性细胞的平均浸润率显著高于PD-L1阴性TC（CD68 p=0.0095；CD163<0.0001）。在多变量逻辑回归分析中，只有CD163阳性细胞的密度与TC细胞中PD-L1的表达相关（OR 1.52；=0.032）。在预后分析中，PD-L1超过10%与短无复发生存期显著相关（HR=2.66；=0.028）。对于CD163巨噬细胞评估，中位数以上的密度也与无复发生存期显著相关（HR=2.48；=0.021）。
结论
CD163 M2样巨噬细胞浸润与CC中PD-L1表达高度相关，提示巨噬细胞浸润可作为潜在的治疗靶点。
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