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北印度人群原发性中枢神经系统弥漫性大 B 细胞淋巴瘤中肿瘤免疫微环境和免疫检查点通路的预后意义

英文原题:Prognostic implications of the tumor immune microenvironment and immune checkpoint pathway in primary central nervous system diffuse large B-cell lymphoma in the North Indian population.

查看英文原题

Prognostic implications of the tumor immune microenvironment and immune checkpoint pathway in primary central nervous system diffuse large B-cell lymphoma in the North Indian population.

PubMed 2021/12/23(内容时间) APMIS Q2 · IF 2.2(JCR 2025)

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中文摘要

原发性中枢神经系统弥漫性大B细胞淋巴瘤(PCNS-DLBCL)是一种罕见的结外恶性淋巴瘤,预后较差。肿瘤微环境(TME)组成及PD-1/PD-L1免疫检查点通路的预后影响在PCNS-DLBCL中仍未确定。

我们旨在量化PCNSL中TIL(肿瘤浸润淋巴细胞)(TILs)、肿瘤相关巨噬细胞(TAMs)及PD-L1表达,并评估其预后意义。纳入7年间所有经组织病理学诊断为PCNS-DLBCL的患者。在组织芯片上进行CD3、CD4、CD8、FOXP3、CD68、CD163、PD-1和PD-L1的免疫组化染色。共纳入44例符合筛选标准的PCNS-DLBCL病例,平均年龄为55 ± 12.3岁,男女比例为0.91:1。平均总生存期(OS)和无病生存期(DFS)分别为531.6天和409.8天。在TILs中,CD3+ T细胞数量增多显示更好的OS和DFS,但未达到统计学显著性。CD4阳性T细胞与更长的OS(p = 0.037)和DFS(p = 0.023)显著相关。TAMs(CD68和CD163阳性)与OS和DFS呈负相关,但未达到统计学显著性(p > 0.05)。免疫细胞中PD-L1表达增高(而非肿瘤细胞中)与显著更好的DFS相关(p = 0.037)。TME在PCNS-DLBCL的预后中发挥重要作用。CD4+ T细胞和表达PD-L1的免疫细胞数量增多与PCNS-DLBCL更好的预后相关。需要更大样本量的进一步研究来评估针对TME的靶向治疗和免疫检查点抑制剂在该疾病中的作用。

展开英文摘要原文

Primary central nervous system-diffuse large B-cell lymphoma (PCNS-DLBCL) is a rare, extranodal malignant lymphoma carrying poor prognosis. The prognostic impact of tumor microenvironment (TME) composition and the PD-1/PD-L1 immune checkpoint pathway are still undetermined in PCNS-DLBCL.

We aimed to quantify the tumor-infiltrating lymphocytes (TILs), tumor-associated macrophages (TAMs), and PD-L1 expression in the PCNSL and evaluated their prognostic significance. All patients with histopathologically diagnosed PCNS-DLBCL over a period of 7 years were recruited. Immunohistochemistry for CD3, CD4, CD8, FOXP3, CD68, CD163, PD-1, and PD-L1 was performed on the tissue microarray. Forty-four cases of PCNS-DLBCL, who satisfied the selection criteria, were included with mean age of 55 ± 12. 3 years and male-to-female ratio of 0. 91:1. The mean overall survival (OS) and disease-free survival (DFS) was 531. 6 days and 409. 8 days, respectively.

Among TILs, an increased number of CD3+ T cells showed better OS and DFS, without achieving statistical significance. CD4 positive T-cells were significantly associated with the longer OS (p = 0. 037) and DFS (p = 0. 023). TAMs (68CD and CD163 positive) showed an inverse relationship with OS and DFS but did not reach statistical significance (p > 0.

05). Increased PD-L1 expression in immune cells, but not in tumor cells, was associated with significantly better DFS (p = 0. 037). The TME plays a significant role in the prognosis of PCNS-DLBCL. Increased number of CD4+ T cells and PD-L1-expressing immune cells is associated with better prognosis in PCNS-DLBCL.

Further studies with larger sample size are required to evaluate the role of targeted therapy against the TME and immune check point inhibitors in this disease.

论文信息

作者
Parkhi M、Chatterjee D、Bal A、Vias P、Yadav BS、Prakash G、Gupta SK、Radotra BD
单位
Department of Histopathology, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh, India.India
期刊
APMIS : acta pathologica, microbiologica, et immunologica Scandinavica2022 Feb
原文标识
PubMed 34862664 · DOI 10.1111/apm.13195