间皮素作为癌症免疫治疗的生物标志物和治疗靶点
Mesothelin as Biomarker and Therapeutic Target for Immunotherapy in Cancer.
癌症仍是一个关键的全球健康问题,原因在于发现晚、耐药和高死亡率。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:High expression of CXCL13 predicts a favorable response to immunotherapy by upregulating CXCR5+CD8+ T-cell infiltration in gastric cancer.
High expression of CXCL13 predicts a favorable response to immunotherapy by upregulating CXCR5+CD8+ T-cell infiltration in gastric cancer.
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本研究确定 CXCL13 是接受 ICI 治疗的 GC 患者的预后因素,强调其通过 CXCR5+CD8+ T 细胞在抗肿瘤微环境中的关键作用。
识别用于免疫检查点抑制剂(ICI)治疗的预测性生物标志物对胃癌(GC)预后至关重要。C-X-C基序趋化因子配体13(CXCL13)通过与其受体CXCR5特异性结合,在免疫调节中发挥重要作用。然而,其在接受ICI治疗的GC患者中的作用、潜在机制及预后意义仍存在争议。
本研究探讨了CXCL13在GC患者中的临床意义及其潜在的免疫调节功能。共分析了来自两个队列的144例接受化疗联合抗PD-1抗体治疗的GC患者。采用免疫组织化学(IHC)和酶联免疫吸附试验评估CXCL13的表达。通过IHC和免疫荧光评估CXCL13、CXCR5、CD8和CD4之间的关联。采用Kaplan-Meier法和Cox比例风险模型进行生存分析。利用皮下异种移植肿瘤小鼠模型研究CXCL13与抗PD-1抗体的治疗反应。
结果提示,CXCL13高表达患者的生存期延长。CXCL13高表达表现出CXCR5+CD8+ T细胞浸润增加,并与更好的结局相关。CXCL13、CXCR5和CD8+ T细胞的联合评估可作为预后的独立预测因素。此外,CXCR5和CD8+ T细胞富集于三级淋巴结构(TLSs)中,在CXCL13高表达的情况下具有预后获益。CXCL13联合抗PD-1治疗可在体内延缓肿瘤生长,导致CXCR5+CD8+ T细胞浸润增加。
This study investigated the clinical significance of CXCL13 and its potential immunomodulatory function in GC patients. A total of 144 GC patients from two cohorts, who received a combination of chemotherapy and anti-PD-1 antibody, were analyzed. The expression of CXCL13 was assessed using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay. Associations between CXCL13, CXCR5, CD8, and CD4 were assessed by IHC and immunofluorescence. Survival analysis was performed using the Kaplan-Meier method and Cox proportional hazards model. The treatment response to CXCL13 and anti-PD-1 antibody was investigated using a subcutaneous xenograft tumor mouse model.
The results suggested that patients with high CXCL13 expression had prolonged survival. High CXCL13 expression exhibited increased infiltration of CXCR5+CD8+ T cells and was associated with better outcomes. The combined assessment of CXCL13, CXCR5, and CD8+ T cells served as an independent predictor of prognosis. Additionally, CXCR5 and CD8+ T cells were enriched in tertiary lymphoid structures (TLSs), which conferred a prognostic benefit in the presence of high CXCL13 expression. CXCL13, in combination with anti-PD-1 therapy, retarded tumor growth in vivo, resulting in increased infiltration of CXCR5+CD8+ T cells. DISCUSSION: This study identified CXCL13 as a prognostic factor in GC patients receiving ICI therapy, emphasizing its critical role in the antitumor microenvironment via CXCR5+CD8+ T cells.
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