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

弥漫性大B细胞淋巴瘤 肿瘤微环境 组织微阵列 川地163 医学 淋巴瘤 免疫系统 CD8型 FOXP3型 原发性中枢神经系统淋巴瘤 免疫检查点 肿瘤科 T细胞 免疫组织化学 人口 癌症研究 病理 生物 免疫学 免疫疗法 表型 基因 环境卫生 生物化学
作者
Mayur Parkhi,Debajyoti Chatterjee,Amanjit Bal,Poorva Vias,Budhi Singh Yadav,Gaurav Prakash,Sunil Gupta,Bishan Dass Radotra
出处
期刊:Apmis [Wiley]
卷期号:130 (2): 82-94 被引量:10
标识
DOI:10.1111/apm.13195
摘要

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.
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