纵向血浆代谢组学指导食管鳞状细胞癌化疗免疫治疗的动态风险评估与饮食调节
Longitudinal Plasma Metabolomics Guides Dynamic Risk Assessment and Dietary Modulation for Esophageal Squamous Cell Cancer Chemoimmunotherapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Immune Cellular Patterns Predicting Lymph Node Status Helps Personalized Management of Stage T1 Esophageal Squamous Cell Carcinoma.
Immune Cellular Patterns Predicting Lymph Node Status Helps Personalized Management of Stage T1 Esophageal Squamous Cell Carcinoma.
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I期食管鳞状细胞癌(ESCC)内镜切除可保留食管完整性,但无法处理区域淋巴结转移(LNM),因此需要新的风险分层策略。本研究旨在表征可预测I期ESCC淋巴结转移的免疫微环境特征,并探讨其对个体化管理的意义。研究分析了938例I期ESCC患者的临床数据,通过生存分析评估临床病理因素(包括LNM和淋巴血管侵犯[LVI])及免疫参数的预后意义;同时采用多重免疫荧光,定量评估肿瘤巢和基质区内免疫细胞的空间分布。
结果显示,LNM和LVI是独立预后决定因素;根据淋巴结状态和LVI分层后,不同患者结局各异:LNM阴性/LVI阴性组无进展生存期和总生存期最佳,而LNM阳性/LVI阳性组结局最差。
值得注意的是,LNM阳性/LVI阴性患者的预后差于LNM阴性/LVI阳性患者(无进展生存期中位数28个月比41个月,P=.003;总生存期35个月比53个月,P<.001)。多重免疫荧光空间分析鉴定出两种与LNM显著相关的免疫特征:(1)肿瘤巢内CD8⁺FOXP3⁺/CD8⁺ T细胞比例升高(P=.001);(2)CD8⁺FOXP3⁻ T细胞与FOXP3⁺细胞的空间邻近程度降低(P<.001)。这些免疫空间特征可作为术前预测LNM的新型生物标志物。将其与临床风险因素结合,有望优化I期ESCC患者在内镜切除和根治性食管切除术之间的治疗决策。
Endoscopic resection preserves esophageal integrity in stage T1 esophageal squamous cell carcinoma (ESCC), but its inability to address regional lymph node metastasis (LNM) necessitates novel strategies for risk stratification.
This study aimed to characterize the immune microenvironmental features predictive of LNM in stage T1 ESCC and explore their implications for personalized management.
We analyzed clinical data from 938 patients with stage T1 ESCC, evaluating the prognostic significance of clinicopathological factors (including LNM and lymphovascular invasion [LVI]) and immune parameters through survival analyses; multiplex immunofluorescence was performed to quantify spatial immune cell distributions within tumor nests and stromal compartments.
As a result, LNM and LVI emerged as independent prognostic determinants; patients stratified by nodal status and LVI revealed distinct outcomes: LNM-/LVI- cohorts exhibited optimal progression-free survival and overall survival, whereas LNM+/LVI+ subgroups had the poorest outcomes.
Notably, LNM+/LVI- patients demonstrated worse prognosis compared with LNM-/LVI+ cases (median progression-free survival, 28 vs 41 months, P = . 003; overall survival, 35 vs 53 months, P < . 001). Multiplex immunofluorescence spatial analysis identified 2 immune signatures strongly associated with LNM: (1) elevated CD8+FOXP3+/CD8+ T-cell ratio within cancer nests (P = . 001) and (2) reduced spatial proximity between CD8+FOXP3- T cells and FOXP3+ cells (P < .
001). The identified immune topographies (CD8+FOXP3+/CD8+ T-cell ratio within cancer nests and spatial proximity between CD8+FOXP3- T cells and FOXP3+ cells) provide novel biomarkers for preoperative LNM prediction. Integration of these immune signatures with clinical risk factors could optimize therapeutic decision-making between endoscopic resection and radical esophagectomy in stage T1 ESCC.
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