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程序性死亡配体-1和CD8肿瘤浸润淋巴细胞(TILs)作为高级别浆液性卵巢癌(HGSC)的预后预测指标

Programmed death ligand-1 and CD8 tumor-infiltrating lymphocytes (TILs) as prognostic predictors in ovarian high-grade serous carcinoma (HGSC).

作者信息

Farrag Mayada Saad, Abdelwahab Khaled, Farrag Nesrine Saad, Elrefaie Waleed Elsayed, Emarah Ziad

机构信息

Department of Pathology, Faculty of Medicine, Port Said University, Port Said, Egypt.

Department of Surgical Oncology, Mansoura Oncology Center, Mansoura University, Mansoura, Egypt.

出版信息

J Egypt Natl Canc Inst. 2021 Jul 9;33(1):16. doi: 10.1186/s43046-021-00073-5.

Abstract

BACKGROUND

P D-L1 is expressed in tumor cells and plays a crucial role in tumor immune escape. Tumor-infiltrating lymphocytes (TILs) as CD8 T cells contribute to reduced tumor growth. Few studies investigated the prognostic effect of PD-L1 and CD8 TILs in ovarian high-grade serous carcinoma (HGSC). In the present study, we analyzed the expression of PD-L1 and CD8 TILs in HGSC by immunohistochemistry, and results were correlated to prognosis. It was carried on 54 cases of ovarian HGSC who attended the Oncology Centre, Mansoura University, Egypt, from 2012 till 2019.

RESULTS

Nearly 60% of cases showed positive PD-L1 expression in tumor cells. Regarding the clinicopathological characteristics, higher PD-L1 expression was found among patients with residual tumor (82.4%) compared to patients with no residual tumor (54.5%), with marginal statistical significance (p 0.07). PD-L1 was significantly associated with CD8 TILs expression. Higher PD-L1 expression was found among tumors with low expression of CD8 TILs with statistically significant difference (p≤0.001). Disease-free survival (DFS) was significantly lower among the group with positive expression of PD-L1 compared to the group with negative expression of PD-L1 (p 0.01), while overall survival (OS) was not associated with PD-L1 expression. On the other hand, the overall survival (OS) in patients with high CD8 expression was significantly higher than patients with low CD8 expression (p 0.043), while DFS was not significantly different among both CD8 TILS groups.

CONCLUSIONS

PD-L1 and CD8 TILs may become a promising therapeutic target for patients with ovarian HGSC. More studies are needed to further validate their prognostic effect. Precise identification of patients who will benefit from PD-L1 checkpoint blockade and TILs adaptive immunotherapy is mandatory.

摘要

背景

程序性死亡配体1(PD-L1)在肿瘤细胞中表达,在肿瘤免疫逃逸中起关键作用。肿瘤浸润淋巴细胞(TILs)作为CD8 T细胞有助于抑制肿瘤生长。很少有研究调查PD-L1和CD8 TILs在卵巢高级别浆液性癌(HGSC)中的预后作用。在本研究中,我们通过免疫组织化学分析了HGSC中PD-L1和CD8 TILs的表达,并将结果与预后相关联。该研究对2012年至2019年在埃及曼苏拉大学肿瘤中心就诊的54例卵巢HGSC患者进行。

结果

近60%的病例显示肿瘤细胞中PD-L1表达呈阳性。关于临床病理特征,与无残留肿瘤的患者(54.5%)相比,残留肿瘤患者中PD-L1表达更高(82.4%),差异具有边际统计学意义(p = 0.07)。PD-L1与CD8 TILs表达显著相关。在CD8 TILs低表达的肿瘤中发现PD-L1表达更高,差异具有统计学意义(p≤0.001)。与PD-L1阴性表达组相比,PD-L1阳性表达组的无病生存期(DFS)显著更低(p = 0.01),而总生存期(OS)与PD-L1表达无关。另一方面,CD8高表达患者的总生存期(OS)显著高于CD8低表达患者(p = 0.043),而两个CD8 TILS组之间的DFS没有显著差异。

结论

PD-L1和CD8 TILs可能成为卵巢HGSC患者有前景的治疗靶点。需要更多研究进一步验证它们的预后作用。必须精确识别将从PD-L1检查点阻断和TILs适应性免疫治疗中获益的患者。

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