Ma Jiajia, Pang Xuelian, Li Junna, Zhang Wei, Cui Wenli
Department of Pathology, The First Affiliated Hospital, Xinjiang Medical University, Xinjiang, Urumqi, China.
Front Oncol. 2022 Dec 6;12:1069378. doi: 10.3389/fonc.2022.1069378. eCollection 2022.
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.
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.
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).
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.
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。
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。
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)。
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。