不适合移植的大 B 细胞淋巴瘤二线使用 axicabtagene ciloleucel：ALYCANTE 最终分析
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CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
弥漫性大 B 细胞淋巴瘤中 PD1、LAG3 和 CTLA4 的免疫组化表达、临床病理相关性及预后价值
英文原题：Immunohistochemical expression of PD1, LAG3, and CTLA4 in diffuse large B cell lymphoma, clinicopathological correlation, and prognostic value.
查看英文原题
Immunohistochemical expression of PD1, LAG3, and CTLA4 in diffuse large B cell lymphoma, clinicopathological correlation, and prognostic value.
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研究概要
PD1 和 LAG3 主要在 TILs 中表达。PD1 表达（在 TILs 和肿瘤细胞中）与延长的 OS 相关，而 LAG3 表达（在肿瘤细胞中）与较短的 DFS 相关，其在 TILs 中的表达倾向于较短的 OS。CTLA4 表达与晚期疾病分期相关，但与 OS 无关。这些发现可能表明，靶向 LAG3 的免疫检查点抑制剂可能通过增强抗肿瘤免疫反应在 DLBCL 中具有治疗潜力。需要进一步研究评估抑制这些检查点分子与现有治疗方式联合的有效性。
研究思路结论见上方概要
背景
肿瘤微环境在弥漫性大B细胞淋巴瘤（DLBCL）的生长和进展中具有重要作用。免疫检查点分子，包括PD1、LAG3和CTLA4，对于调节肿瘤微环境中T细胞的功能至关重要。探索这些分子在DLBCL微环境中的表达，对于开发增强抗肿瘤免疫反应的靶向治疗至关重要。
目的
本研究旨在评估DLBCL中PD1、LAG3和CTLA4的免疫组化（IHC）表达，评估其表达与不同临床病理参数的关系，并评价其预后意义。
方法
这项回顾性研究纳入了103例诊断为de novo DLBCL的病例。收集了临床病理和生存数据。进行了PD1、LAG3和CTLA4的IHC检测。
结果
在68.9%（71/103）、82.5%（85/103）和92.2%（95/103）的DLBCL病例中，分别观察到TIL（肿瘤浸润淋巴细胞）（TILs）中PD1、LAG3和CTLA4阳性反应。在单变量分析中，TILs中PD1表达与丙型肝炎病毒（HCV）阳性及延长的总生存期（OS）显著相关。TILs中LAG3表达与IPI评分显著相关，并倾向于较短的OS（无统计学显著性）。肿瘤细胞中LAG3表达与较短的无病生存期（DFS）显著相关。TILs中CTLA4表达与晚期疾病分期（III/IV）显著相关。
展开英文摘要原文
BACKGROUND
The tumor microenvironment has an important role in the growth and progression of diffuse large B-cell lymphoma (DLBCL). Immune checkpoint molecules, including PD1, LAG3, and CTLA4, are crucial to regulate the T cells function in the tumor microenvironment. Exploring the expression of these molecules in DLBCL microenvironment is crucial for developing targeted therapies enhancing anti-tumor immune responses. AIM: This study aims to evaluate the immunohistochemical (IHC) expression of PD1, LAG3, and CTLA4 in DLBCL, assess the relation of their expression to different clinicopathological parameters and evaluate their prognostic significance.
METHODS
This retrospective study encompassed 103 cases diagnosed as de novo DLBCL. Clinicopathologic and survival data were gathered. IHC for PD1, LAG3, and CTLA4 was performed.
RESULTS
PD1, LAG3, and CTLA4 positive reaction was observed in tumor-infiltrating lymphocytes (TILs) in 68.9% (71/103), 82.5% (85/103), and 92.2% (95/103) of DLBCL cases, respectively. PD1 expression in TILs was significantly associated with hepatitis C virus (HCV) positivity and prolonged overall survival (OS) in univariate analysis. LAG3 expression in TILs was significantly associated with IPI score and tended towards shorter OS (not statistically significant). LAG3 expression in tumor cells was significantly associated with shorter disease-free survival (DFS). CTLA4 expression in TILs was significantly associated with advanced disease stage (III/IV).
CONCLUSION
PD1 and LAG3 are expressed mainly in TILs. PD1 expression (in TILs and tumor cells) is associated with prolonged OS, while LAG3 expression (in tumor cells) is associated with shorter DFS and its expression in TILs tended towards shorter OS. CTLA4 expression is associated with advanced disease stage but not associated with OS. These findings may suggest that immune checkpoint inhibitors targeting LAG3 may offer therapeutic potential in DLBCL by enhancing the antitumor immune response. Additional research is needed to assess the effectiveness of inhibition of these checkpoint molecules in combination with existing treatment modalities.
论文信息
- 作者
- William MI、Tantawy DA、Elsergany AR、El-Hawary AK、Yussif SM
- 单位
- Mansoura University, Al Mansurah, Egypt. madonna@mans.edu.eg.Egypt
- 期刊
- Journal of the Egyptian National Cancer Institute2025 Jun 7
- 原文标识
- PubMed 40481915 · DOI 10.1186/s43046-025-00303-0
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