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:Comprehensive Analysis of Tumor Microenvironment and PD-L1 Expression Associations with Clinicopathological Features and Prognosis in Diffuse Large B-Cell Lymphoma.
Comprehensive Analysis of Tumor Microenvironment and PD-L1 Expression Associations with Clinicopathological Features and Prognosis in Diffuse Large B-Cell Lymphoma.
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TME 在 DLBCL 的生物学行为中起着关键作用,尤其是因为 TIL-T 和 TAMs 与患者生存结局显著相关。
本回顾性研究评估89例原发性DLBCL病例,结合临床病理资料,通过自动化免疫组织化学定量分析肿瘤热点区和微环境区CD3、CD8、FOXP3、CD163及PD-L1表达。采用Kaplan-Meier法和Cox回归分析TIL-T、TAM、PD-L1表达与无进展生存期(PFS)和总生存期(OS)的预后相关性。
CD3+细胞浸润高与Ki-67表达低相关;FOXP3+细胞水平升高与美国东部肿瘤协作组体能状态(ECOG)改善相关。CD163+ TAM水平因NCCN-IPI风险、ECOG和细胞起源而异。肿瘤细胞PD-L1(nPD-L1)阳性与NCCN-IPI评分较高、CD3+ T细胞浸润和CD163+ TAM富集相关。微环境PD-L1(mPD-L1)与年龄、ECOG、B症状及所有T细胞亚群和TAM浸润相关。生存分析显示,CD3+、CD8+和FOXP3+ TIL-T水平较高、CD163+ TAM较多或mPD-L1阳性均与OS延长相关;CD3+浸润和mPD-L1阳性与PFS改善相关。单变量分析发现,B症状、结外受累和TIL-T水平低是OS风险因素,而ECOG 0和mPD-L1阳性具有保护作用。多变量模型证实B症状、结外病变和CD3+ TIL-T是OS独立预测因素;CD3+ TIL-T和B症状独立影响PFS。 讨论:TME对DLBCL生物学行为至关重要,尤其是TIL-T和TAM与患者生存结局显著相关。这些细胞可作为关键生物标志物,并为DLBCL提供新的免疫治疗靶点。
This retrospective study evaluated 89 primary DLBCL cases, integrating clinicopathological data with automated immunohistochemical quantification of CD3, CD8, FOXP3, CD163, and PD-L1 expression in tumor hotspots and microenvironmental compartments. Prognostic associations of TIL-T, TAMs, and PD-L1 expression with PFS and OS were analyzed via Kaplan-Meier methods and Cox regression.
High CD3+ infiltration correlated with lower Ki-67 expression, while elevated FOXP3+ levels linked to improved Eastern Cooperative Oncology Group Performance Status (ECOG). CD163+ TAMs varied by NCCN-IPI risk, ECOG, and cell of origin. Neoplastic PD-L1 (nPD-L1) positivity associated with higher NCCN-IPI scores, CD3+ T-cell infiltration, and CD163+ TAM enrichment. Microenvironmental PD-L1 (mPD-L1) correlated with age, ECOG, B symptoms, and infiltration of all T-cell subsets and TAMs. Survival analysis revealed prolonged overall survival (OS) with high CD3+, CD8+, FOXP3+ TIL-T, CD163+ TAMs, or mPD-L1 positivity, while progression-free survival (PFS) improved with CD3+ infiltration and mPD-L1. Univariate analysis identified B symptoms, extranodal involvement, and low TIL-T levels as OS risks, whereas ECOG 0 and mPD-L1+ were protective. Multivariate modeling confirmed B symptoms, extranodal disease, and CD3+ TIL-T as independent OS predictors; CD3+ TIL-T and B symptoms independently impacted PFS. DISCUSSION: The TME plays a crucial role in the biological behavior of DLBCL, particularly because TIL-T and TAMs are significantly associated with patient survival outcomes. These cell types may serve as critical biomarkers and provide novel immunotherapy targets in DLBCL.
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