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弥漫大B细胞淋巴瘤肿瘤免疫微环境中免疫检查点的表达:临床病理特征与预后

The immune checkpoint expression in the tumor immune microenvironment of DLBCL: Clinicopathologic features and prognosis.

作者信息

Ma Jiajia, Pang Xuelian, Li Junna, Zhang Wei, Cui Wenli

机构信息

Department of Pathology, The First Affiliated Hospital, Xinjiang Medical University, Xinjiang, Urumqi, China.

出版信息

Front Oncol. 2022 Dec 6;12:1069378. doi: 10.3389/fonc.2022.1069378. eCollection 2022.

Abstract

BACKGROUND & AIMS: The immune checkpoint recently provides a new strategy for the immunotherapy of malignant tumors. However, the role in the immune microenvironment of DLBCL is not completely clear.

METHODS

We detected the expression of PD-1, LAG-3, TIM-3, and TIGIT on TILs and on tumor cells among 174 DLBCL patients by IHC.

RESULTS

In TILs, the positive rates of PD-1, LAG-3, TIM-3 and TIGIT were 79.3%, 78.8%, 62.7% and 69.5%, respectively.TIM-3 and TIGIT were expressed in 44.8% and 45.4% of tumor cells. The expression of TIM-3 in TILs was significantly correlated with the Ann-Arbor stage (P=0.039). There was a positive correlation Between PD-1 and LAG-3 or TIM-3 and TIGIT.In addition, LAG-3 expression in TILs was associated with inferior prognosis.Multivariate analysis showed that PS score and R-CHOP therapy were independent risk factors for OS and PFS in patients with DLBCL (P=0.000).

CONCLUSIONS

The expression level of TIM-3 is closely related to the Ann-Arbor stage, which may be expected to be a new index to evaluate the invasiveness of DLBCL. PD-1 was correlated with the expression of LAG-3, and the high expression of LAG-3 and LAG-3/PD-1 predicted the poor prognosis of DLBCL. Therefore, LAG-3 may become a new target of immunotherapy, or be used in combination with PD-1 inhibitors to improve the drug resistance of current patients with DLBCL.

摘要

背景与目的

免疫检查点最近为恶性肿瘤的免疫治疗提供了一种新策略。然而,其在弥漫性大B细胞淋巴瘤(DLBCL)免疫微环境中的作用尚不完全清楚。

方法

我们通过免疫组化检测了174例DLBCL患者肿瘤浸润淋巴细胞(TILs)及肿瘤细胞上PD-1、LAG-3、TIM-3和TIGIT的表达。

结果

在TILs中,PD-1、LAG-3、TIM-3和TIGIT的阳性率分别为79.3%、78.8%、62.7%和69.5%。TIM-3和TIGIT在44.8%和45.4%的肿瘤细胞中表达。TILs中TIM-3的表达与Ann-Arbor分期显著相关(P=0.039)。PD-1与LAG-3、TIM-3与TIGIT之间呈正相关。此外,TILs中LAG-3的表达与预后较差相关。多因素分析显示,PS评分和R-CHOP治疗是DLBCL患者总生存期(OS)和无进展生存期(PFS)的独立危险因素(P=0.000)。

结论

TIM-3的表达水平与Ann-Arbor分期密切相关,有望成为评估DLBCL侵袭性的新指标。PD-1与LAG-3的表达相关,LAG-3及LAG-3/PD-1的高表达预示着DLBCL预后不良。因此,LAG-3可能成为免疫治疗的新靶点,或与PD-1抑制剂联合使用以改善当前DLBCL患者的耐药性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f44/9763555/55c663b51f16/fonc-12-1069378-g001.jpg

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