Combined tumor-associated macrophages biomarker predicting extremely poor outcome of patients with primary central nervous system lymphoma
Combined tumor-associated macrophages biomarker predicting extremely poor outcome of patients with primary central nervous system lymphoma
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联合肿瘤相关巨噬细胞生物标志物预测原发性中枢神经系统淋巴瘤患者预后极差
DOI：
10.1002/hon.2926
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发表时间：
2021
影响因子：
3.3
通讯作者：
Li Zhiming
中科院分区：
文献类型：
--
作者：
Sun Xiaoqing;Wang Caiqin;Chen Cui;Huang Jiajia;Wu Xianqiu;Wang Yu;He Xiaohua;Cao Jianghua;Jiang Wenqi;Sun Peng;Li Zhiming
原发性中枢神经系统淋巴瘤（PCNSL）是一种侵袭性强、预后差的罕见恶性肿瘤.然而，在临床实践中没有可靠的PCNSL预后生物标志物。在这里，我们的目的是确定一个可靠的预后生物标志物预测PCNSL患者的生存。在这项研究中，多重免疫荧光和数字成像分析用于表征肿瘤相关巨噬细胞（TAM）免疫表型和TAM上程序性细胞死亡配体1的表达，以及59例PCNSL患者诊断性肿瘤组织样本的预后。我们发现，M2与M1的比值是PCNSL比M1样或M2样巨噬细胞浸润更可靠的预后生物标志物。此外，TAM上的程序性死亡配体1（PD-L1）表达和PCNSL中的M2/M1比值的组合证明了比PD-L1阳性TAM或M2/M1比值更好的预后区分性能。为了验证组合TAM相关生物标志物的预后意义，将其整合到国际结外淋巴瘤研究组（IELSG）指数中，并称为IELSG-M指数。Kaplan-Meier曲线显示，IELSG-M指数可以将患者区分为低风险、中等风险或高风险亚组，在预后方面优于IELSG。总生存期的IELSG-M受试者工作特征曲线下面积为0.844;上级于IELSG模型（0.580）。总之，本研究的结果表明，TAM上的PD-L1和M2/M1比值的组合可能是PCNSL的强预后预测生物标志物，IELSG-M指数比IELSG指数具有更好的预后意义。
Primary central nervous system lymphoma (PCNSL) is an aggressive and rare malignancy with poor prognosis. However, there are no reliable prognostic biomarkers for PCNSL in clinical practice. Here, we aimed to identify a reliable prognostic biomarker for predicting the survival of PCNSL patients. In this study, multiplex immunofluorescence and digital imaging analysis were used to characterize tumor‐associated macrophages (TAMs) immunophenotypes and the expression of programmed cell death ligand 1 on TAMs, with regard to prognosis from diagnostic tumor tissue samples of 59 PCNSL patients. We found that the M2‐to‐M1 ratio was a more reliable prognostic biomarker for PCNSL than M1‐like or M2‐like macrophage infiltration. In addition, the combination of programmed death‐ligand 1 (PD‐L1) expression on TAMs and the M2‐to‐M1 ratio in PCNSL demonstrated improved performance in prognostic discrimination than PD‐L1‐positive TAMs or M2‐to‐M1 ratio. To validate the prognostic significance of the combined TAMs associated biomarkers, they were integrated into the International Extranodal Lymphoma Study Group (IELSG) index and termed as IELSG‐M index. Kaplan–Meier plots showed that the IELSG‐M index could discriminate patients into low‐, intermediate‐ or high‐risk subgroups, better than IELSG, in terms of prognosis. The areas under the receiver operating characteristic curves of IELSG‐M was 0.844 for overall survival; superior to the IELSG model (0.580). Taken together, this study's findings showed that the combination of PD‐L1 on TAMs and the M2‐to‐M1 ratio could be strong prognostic predictive biomarkers for PCNSL and the IELSG‐M index had improved prognostic significance than the IELSG index.