PD1、LAG3和CTLA4在弥漫性大B细胞淋巴瘤中的免疫组化表达、临床病理相关性及预后价值
Immunohistochemical expression of PD1, LAG3, and CTLA4 in diffuse large B cell lymphoma, clinicopathological correlation, and prognostic value.
作者信息
William Madonna I, Tantawy Dina A, Elsergany Alyaa R, El-Hawary Amira K, Yussif Shaimaa M
机构信息
Mansoura University, Al Mansurah, Egypt.
出版信息
J Egypt Natl Canc Inst. 2025 Jun 7;37(1):47. doi: 10.1186/s43046-025-00303-0.
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.
背景
肿瘤微环境在弥漫性大B细胞淋巴瘤（DLBCL）的生长和进展中起重要作用。免疫检查点分子，包括PD1、LAG3和CTLA4，对于调节肿瘤微环境中的T细胞功能至关重要。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PD1、LAG3和CTLA4在DLBCL中的免疫组化（IHC）表达，评估其表达与不同临床病理参数的关系，并评估其预后意义。
方法
这项回顾性研究纳入了103例诊断为初治DLBCL的病例。收集临床病理和生存数据。进行了PD1、LAG3和CTLA4的免疫组化检测。
结果
在分别为68.9%（71/103）、82.5%（85/103）和92.2%（95/103）的DLBCL病例的肿瘤浸润淋巴细胞（TILs）中观察到PD1、LAG3和CTLA4阳性反应。单因素分析显示，TILs中PD1表达与丙型肝炎病毒（HCV）阳性及总生存期（OS）延长显著相关。TILs中LAG3表达与国际预后指数（IPI）评分显著相关，且OS有缩短趋势（无统计学意义）。肿瘤细胞中LAG3表达与无病生存期（DFS）缩短显著相关。TILs中CTLA4表达与疾病晚期（III/IV期）显著相关。
结论
PD1和LAG3主要在TILs中表达。PD1表达（在TILs和肿瘤细胞中）与OS延长相关，而LAG3表达（在肿瘤细胞中）与DFS缩短相关，其在TILs中的表达有OS缩短趋势。CTLA4表达与疾病晚期相关，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应用的有效性。
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