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
弥漫性大 B 细胞淋巴瘤中的 LAG-3：免疫组化表达模式与临床病理相关性
英文原题：LAG-3 in Diffuse Large B-Cell Lymphoma: Immunohistochemical Expression Patterns and Clinicopathological Correlations.
查看英文原题
LAG-3 in Diffuse Large B-Cell Lymphoma: Immunohistochemical Expression Patterns and Clinicopathological Correlations.
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中文摘要
方法
这项回顾性、单中心研究纳入2007年至2019年间诊断的210例DLBCL患者。采用免疫组化方法在全组织切片上评估LAG-3表达。肿瘤细胞表达根据阳性细胞的百分比和强度进行评估，而LAG-3阳性TILs则定量为每个高倍视野（HPF）阳性淋巴细胞的平均数量。分析其与临床病理参数、治疗反应、总生存期和无进展生存期（PFS）的关联。
结果
在177例（84.3%）的肿瘤细胞中观察到不同强度的LAG-3染色，采用10%肿瘤细胞作为截断值时，82例（39.0%）被判定为LAG-3阳性。LAG-3阳性TILs的中位数为5/HPF。男性患者LAG-3阳性肿瘤细胞的百分比高于女性患者（p = 0.039）。在LAG-3阳性TILs >5/HPF的病例中，中度至强肿瘤细胞染色显著比TILs ≤5/HPF的病例更常见（p = 0.018）。LAG-3表达参数与治疗反应或总生存期无显著关联。单因素Cox回归分析也未显示总生存期与LAG-3阳性TIL计数、肿瘤细胞LAG-3百分比或染色强度之间存在显著关联。在66例可评估患者中进行的探索性PFS分析也显示与LAG-3表达参数无显著关联。
结论
DLBCL中LAG-3表达既见于肿瘤细胞，也见于TIL。LAG-3阳性TIL增多与肿瘤细胞表达较强之间的关联，支持在两种细胞区室中进一步研究LAG-3。在本队列中未观察到与总生存期存在显著关联；然而，生存事件数量有限，无法就其预后意义得出确定性结论。有必要采用标准化评估方法并纳入更大规模、临床特征明确的队列开展进一步研究。
展开英文摘要原文
Background/Objectives: Lymphocyte activation gene-3 (LAG-3) is an inhibitory immune checkpoint molecule that may contribute to immune escape in diffuse large B-cell lymphoma (DLBCL).
This study aimed to characterize LAG-3 expression in neoplastic cells and tumor-infiltrating lymphocytes (TILs) and to investigate its associations with clinicopathological features and clinical outcome. Methods: This retrospective, single-center study included 210 patients with DLBCL diagnosed between 2007 and 2019. LAG-3 expression was evaluated immunohistochemically in whole-tissue sections. Tumor-cell expression was assessed according to the percentage and intensity of positive cells, while LAG-3-positive TILs were quantified as the mean number of positive lymphocytes per high-power field (HPF). Associations with clinicopathological parameters, treatment response, overall survival, and progression-free survival (PFS) were analyzed. Results: LAG-3 staining of varying intensity was observed in neoplastic cells in 177 cases (84. 3%), and 82 cases (39. 0%) were classified as LAG-3 positive using a 10% tumor-cell cut-off. The median number of LAG-3-positive TILs was 5/HPF. Male patients showed a higher percentage of LAG-3-positive tumor cells than female patients ( p = 0.
039). Moderate-to-strong tumor-cell staining was significantly more frequent in cases with >5 LAG-3-positive TILs/HPF than in those with ≤5 TILs/HPF ( p = 0. 018). LAG-3 expression parameters were not significantly associated with treatment response or overall survival. Univariate Cox regression analysis also showed no significant association between overall survival and LAG-3-positive TIL count, tumor-cell LAG-3 percentage, or staining intensity.
Exploratory PFS analysis in 66 evaluable patients also showed no significant association with LAG-3 expression parameters. Conclusions: LAG-3 expression in DLBCL occurs in both neoplastic cells and TILs.
The association between increased LAG-3-positive TILs and stronger tumor-cell expression supports further investigation of LAG-3 across both cellular compartments. No significant association with overall survival was observed in this cohort; however, the limited number of survival events precludes definitive conclusions regarding its prognostic significance.
Further studies using standardized assessment methods and larger, clinically well-characterized cohorts are warranted.
论文信息
- 作者
- Doğan M、Coşkun EB、Bakırtaş M、Coşkun A、Kandemir O
- 第一作者单位
- Department of Pathology, Ankara Bilkent City Hospital, Ankara Yıldırım Beyazıt University, Ankara 06800, Türkiye.Turkey
- 通讯作者单位
- Department of Pathology, Etlik City Hospital, Ankara 06010, Türkiye.Turkey
- 期刊
- Journal of clinical medicine2026 Sep 5
- 原文标识
- PubMed 42739890 · DOI 10.3390/jcm15176888
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