Qiu Meng-Jun, Xia Qin, Chen Yao-Bing, Fang Xie-Fan, Li Qiu-Ting, Zhu Li-Sheng, Jiang Xin, Xiong Zhi-Fan, Yang Sheng-Li
Division of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Institute of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Oncol. 2021 Apr 15;11:600238. doi: 10.3389/fonc.2021.600238. eCollection 2021.
In recent years, immune checkpoint inhibitors have shown significant effects in a variety of solid tumors. However, due to the low incidence of small cell lung cancer (SCLC) and its unclear mechanism, immune checkpoints in SCLC have not been fully studied.
We evaluated the expression of PD-L1, B7-H3, and B7-H4 in 115 SCLC tissue specimens using immunohistochemistry. The clinical data of patients with SCLC were retrospectively reviewed to investigate three negative co-stimulatory B7 family molecules' ability to affect the prognosis of SCLC.
Among the SCLC patients with complete follow-up data (n = 107), sixty-nine (64.49%) expressed moderate to high B7-H3 levels, which correlated positively with tumor sizes ( < 0.001). Eighty (74.77%) patients expressed moderate to high B7-H4 levels, which correlated positively with metastases ( = 0.049). The positive expression of B7-H3 and B7-H4 correlated significantly with shortened overall survival (OS) (B7-H3, = 0.006; B7-H4, = 0.019). PD-L1 was positively expressed only in 13.08% of cancer tissues, and there was no significant correlation with prognosis. The Cox proportional hazards regression showed that B7-H3 was an independent prognostic indicator of OS ( = 0.028; HR = 2.125 [95% CI = 0.985-4.462]).
Our results suggest that B7-H3 has a negative predictive effect on SCLC. This outcome provides a theoretical basis for the subsequent research on immune checkpoint inhibitors targeting B7-H3.
近年来,免疫检查点抑制剂在多种实体瘤中显示出显著疗效。然而,由于小细胞肺癌(SCLC)发病率低且其机制尚不清楚,SCLC中的免疫检查点尚未得到充分研究。
我们采用免疫组织化学方法评估了115例SCLC组织标本中PD-L1、B7-H3和B7-H4的表达情况。回顾性分析SCLC患者的临床资料,以研究三种负性共刺激B7家族分子影响SCLC预后的能力。
在有完整随访数据的SCLC患者中(n = 107),69例(64.49%)表达中度至高度B7-H3水平,其与肿瘤大小呈正相关(<0.001)。80例(74.77%)患者表达中度至高度B7-H4水平,其与转移呈正相关(=0.049)。B7-H3和B7-H4的阳性表达与总生存期(OS)缩短显著相关(B7-H3,=0.006;B7-H4,=0.019)。PD-L1仅在13.08%的癌组织中呈阳性表达,与预后无显著相关性。Cox比例风险回归显示,B7-H3是OS的独立预后指标(=0.028;HR = 2.125 [95% CI = 0.985 - 4.462])。
我们的结果表明,B7-H3对SCLC具有负性预测作用。这一结果为后续针对B7-H3的免疫检查点抑制剂研究提供了理论依据。