免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:The Prognostic Role of CD8(+) Tumor-Infiltrating Lymphocyte Density in Head and Neck Mucosal Melanoma.
The Prognostic Role of CD8(+) Tumor-Infiltrating Lymphocyte Density in Head and Neck Mucosal Melanoma.
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自动化数字 CD8 + TIL 密度计数是评估 HNMM 患者 TIL 密度的可靠方法。高 CD8 + TIL 密度是与改善 RFS 相关的独立因素,并倾向于改善 OS。
探讨使用自动化、定量、基于免疫组织化学的方法评估CD8+TIL(肿瘤浸润淋巴细胞)密度在头颈部黏膜黑色素瘤(HNMM)中的预后作用。
回顾性队列研究。单中心、三级甲等医院。纳入2002年1月至2021年12月在匹兹堡大学接受治疗的45例原发性HNMM患者。对于有充足原发肿瘤标本的患者,使用自动化图像分析算法在数字化切片上量化CD8 + TIL密度。使用受试者工作特征曲线确定生物标志物截断值。以无复发生存期(RFS)和总生存期(OS)为终点,采用Kaplan-Meier法和Cox比例风险模型进行生存分析。
34例患者有足够的病理标本可用于分析。CD8+ TIL密度阈值为373.6个/mm²最能根据生存结局区分患者。在log-rank检验中,与TIL低患者相比,TIL高患者的5年RFS(p = 0.06)和OS(p = 0.074)有改善趋势。采用多因素分析,高TIL密度与RFS改善显著相关(风险比[HR](95%置信区间[CI]):0.17(0.03-0.83),p = 0.028),但与OS改善无关(HR(95% CI):0.48(0.08-2.90),p = 0.4)。肿瘤特征,如晚期淋巴结分期(HR(95% CI):13.2(1.68-104),p = 0.014)和存在转移性疾病(HR(95% CI):48.2(1.94-1196),p = 0.018),与RFS恶化相关。
To explore the prognostic role of CD8+ tumor-infiltrating lymphocytes (TIL) density in head and neck mucosal melanoma (HNMM) using an automated, quantitative, immunohistochemistry-based methodology. STUDY DESIGN: Retrospective cohort study. SETTING: Single-institution, tertiary care hospital.
Forty-five patients with primary HNMM treated between January 2002 and December 2021 at the University of Pittsburgh were included. For patients with ample primary tumor specimens, CD8 + TIL density was quantified using an automated image analysis algorithm on digitized slides. Receiver operating characteristic curves were used to delineate a biomarker cutoff. Survival analysis using the Kaplan-Meier method and Cox proportional hazards was performed with recurrence-free survival (RFS) and overall survival (OS) as endpoints.
Thirty-four patients had adequate pathologic specimens available for analysis. CD8 + TIL density threshold of 373.6 cells/mm 2 best delineated patients based on survival outcomes. On log-rank testing, TIL high patients trended toward improved 5-year RFS (p = 0.06) and OS (p = 0.074) when compared to TIL low patients. Using multivariate analysis, high TIL density was significantly associated with improved RFS (hazard ratio [HR] (95% confidence interval [CI]): 0.17 (0.03-0.83), p = 0.028) but not improved OS (HR (95% CI): 0.48 (0.08-2.90), p = 0.4). Tumor characteristics such as advanced nodal staging (HR (95% CI): 13.2 (1.68-104), p = 0.014), and presence of metastatic disease (HR (95% CI): 48.2 (1.94-1196), p = 0.018) were associated with worsened RFS.
Automated, digital CD8 + TIL density enumeration is a reliable method of assessing TIL density in HNMM patients. High CD8 + TIL density is an independent factor associated with improved RFS and trended toward improved OS.
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