为肝细胞癌武装 GPC3 CAR-T 细胞:多少才足够,下一步是什么?
Armouring GPC3 CAR T cells for hepatocellular carcinoma: how much is enough and what comes next?
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Identification of prognostic risk model based on plasma cell markers in hepatocellular carcinoma through single-cell sequencing analysis.
Identification of prognostic risk model based on plasma cell markers in hepatocellular carcinoma through single-cell sequencing analysis.
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肝细胞癌(HCC)是全球重大健康负担。肿瘤浸润 B 淋巴细胞(TIL-B)可促进肿瘤进展,并显著影响肿瘤治疗疗效。然而,HCC 中 TIL-B 的特征及其对 HCC 治疗的影响仍不清楚。研究采用单细胞 RNA 测序(scRNA-seq)调查 HCC 中 TIL-B 的异质性、细胞分化及细胞间通讯。
此外,使用癌症基因组图谱肝细胞癌(TCGA-LIHC)和肝癌研究所(LCI)队列,建立并验证基于浆细胞标志物的预后风险模型。通过 OncoPredict 和肿瘤免疫功能障碍与排斥(TIDE)算法,估算预后风险模型与 HCC 患者免疫治疗及化疗敏感性的关系。
最后建立列线图和校准曲线,评估风险评分预测生存概率的精确度。研究识别出 HCC 中 5 种 TIL-B 亚型,各自在肿瘤组织中的浸润水平不同。TIL-B 与其他细胞类型之间的相互作用参与塑造不同的肿瘤微环境(TME)。
此外,各 TIL-B 亚型在 HCC 患者中的预后价值不同。该预后风险模型对总生存期具有出色预测准确性,并可区分 HCC 患者对免疫治疗和化疗的不同敏感性。研究数据显示,风险评分是独立预后预测因素,列线图结果进一步证实了其较强的预后能力。
本研究揭示 TIL-B 的异质性,并在 HCC 中建立基于浆细胞标志物的预后风险模型,有望用于预测预后并指导患者选择合适的治疗。
Hepatocellular carcinoma (HCC) represents a substantial global health burden. Tumorinfiltrating B lymphocytes (TIL-Bs) contribute to tumor progression and significantly impact the efficacy of tumor therapy.
However, the characteristics of TIL-Bs in HCC and their effect on HCC therapy remain elusive. Single-cell RNA sequencing (scRNAseq) was applied to investigate the heterogeneity, cellular differentiation and cell-cell communication of TIL-Bs in HCC.
Further, the Cancer Genome Atlas-liver hepatocellular carcinoma (TCGA-LIHC) and liver cancer institutes (LCI) cohorts were applied to construct and validate the plasma cell marker-based prognostic risk model. The relationship between the prognostic risk model and the responsiveness of immunotherapy and chemotherapy in patients with HCC were estimated by OncoPredict and tumor immune dysfunction and exclusion (TIDE) algorithm.
Finally, we established nomogram and calibration curves to evaluate the precision of the risk score in predicating survival probability.
Our data identified five subtypes of TIL-Bs in HCC, each exhibiting varying levels of infiltration in tumor tissues. The interactions between TIL-Bs and other cell types contributed to shaping distinct tumor microenvironments (TME).
Moreover, we found that TIL-Bs subtypes had disparate prognostic values in HCC patients. The prognostic risk model demonstrated exceptional predictive accuracy for overall survival and exhibited varying sensitivities to immunotherapy and chemotherapy among patients with HCC.
Our data demonstrated that the risk score stood as an independent prognostic predictor and the nomogram results further affirmed its strong prognostic capability.
This study reveals the heterogeneity of TIL-Bs and provides a prognostic risk model based on plasma cell markers in HCC, which could prove valuable in predicting prognosis and guiding the choice of suitable therapies for patients with HCC.
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