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原发性 PDGFRA 突变型胃肠道间质瘤中的免疫细胞浸润和 PD-1、PD-L1 的表达。

Immune Cell Infiltration and the Expression of PD-1 and PD-L1 in Primary PDGFRA-Mutant Gastrointestinal Stromal Tumors.

机构信息

Department of General Surgery, Zhongshan Hospital, Fudan University School of Medicine, #180 Fenglin Road, Shanghai, 200032, China.

Department of Pathology, Zhongshan Hospital, Fudan University School of Medicine, #180 Fenglin Road, Shanghai, 200032, China.

出版信息

J Gastrointest Surg. 2021 Aug;25(8):2091-2100. doi: 10.1007/s11605-020-04860-8. Epub 2020 Nov 9.

Abstract

PURPOSE

To characterize the immune cell profile and expression of PD-1, PD-L1, and IDO in PDGFRA-mutant gastrointestinal stromal tumors (GISTs).

METHODS

The clinicopathological data of PDGFRA-mutant GIST patients who received surgical resection in Zhongshan Hospital between January 2013 and August 2019 were reviewed retrospectively. The specimens of tissue chips were detected for immune cell infiltration and the expression of PD-1, PD-L1, and IDO by immunohistochemical staining.

RESULTS

CD3, CD8, and CD68 cells were the main infiltrating immune cells in the 42 patients included in this study. In addition, CD4, CD56, Foxp3, and CD20 cells were also observed. A higher CD8 T cell count was associated with smaller tumor size and PDGFRA D842V mutation (P = 0.047, P = 0.005). A higher CD3 and CD68 cell count was associated with a higher mitotic index (P = 0.022, P = 0.006). CD4 and CD20 cell count was associated with tumor morphology (P = 0.002, P = 0.045). PD-1 expression was present in 37 (88%) samples. Eighteen samples were positive for PD-L1 expression, and it was higher in small vs. large tumors (P = 0.012) and epithelioid and mixed cell type vs. spindle cell type GISTs (P = 0.046). IDO expression was positive in all 42 patients. The number of CD4 cells was significantly greater in the specimens with high IDO expression (P = 0.012).

CONCLUSION

There were abundant infiltrating immune cells in PDGFRA-mutant GISTs. PD-L1 expression was negatively associated with tumor size. The immunotherapy targeting PD-1/PD-L1 checkpoint and IDO may be valuable.

摘要

目的

分析 PDGFRA 突变胃肠间质瘤(GIST)的免疫细胞特征及 PD-1、PD-L1 和 IDO 的表达。

方法

回顾性分析 2013 年 1 月至 2019 年 8 月在中山大学附属中山医院接受手术治疗的 PDGFRA 突变 GIST 患者的临床病理资料,应用免疫组化染色检测组织芯片中免疫细胞浸润情况及 PD-1、PD-L1 和 IDO 的表达。

结果

本研究共纳入 42 例患者,主要浸润免疫细胞包括 CD3、CD8 和 CD68,还观察到 CD4、CD56、Foxp3 和 CD20 细胞。CD8 T 细胞计数较高与肿瘤体积较小和 PDGFRA D842V 突变相关(P=0.047,P=0.005)。CD3 和 CD68 细胞计数较高与有丝分裂指数较高相关(P=0.022,P=0.006)。CD4 和 CD20 细胞计数与肿瘤形态相关(P=0.002,P=0.045)。37 例(88%)样本 PD-1 表达阳性,18 例(43%)样本 PD-L1 表达阳性,小肿瘤的 PD-L1 表达阳性率高于大肿瘤(P=0.012),上皮样和混合细胞型 GIST 的 PD-L1 表达阳性率高于梭形细胞型 GIST(P=0.046)。42 例样本 IDO 表达均为阳性。高 IDO 表达组的 CD4 细胞数量明显更多(P=0.012)。

结论

PDGFRA 突变 GIST 中有丰富的浸润免疫细胞,PD-L1 表达与肿瘤大小呈负相关。针对 PD-1/PD-L1 检查点和 IDO 的免疫治疗可能具有潜在价值。

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