不适合移植的大 B 细胞淋巴瘤二线使用 axicabtagene ciloleucel:ALYCANTE 最终分析
Second-line axicabtagene ciloleucel in large B-cell lymphoma ineligible for transplantation: ALYCANTE final analysis.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
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.
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.
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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。
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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