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:CXCL1 and CXCL6 Are Potential Predictors for HCC Response to TACE.
CXCL1 and CXCL6 Are Potential Predictors for HCC Response to TACE.
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肝细胞癌(HCC)不同的免疫特征可能影响经动脉化疗栓塞(TACE)的疗效。本研究探索性分析TACE应答者与无应答者的肿瘤组织,寻找可预测疗效的新型预后生物标志物。研究回顾性纳入2019年1月至11月连续接受三次TACE的15例HCC患者,其中8例应答、7例无应答,均按mRECIST标准有可测量病灶。研究使用NanoString nCounter泛癌免疫分析面板进行差异表达分析。TACE应答者的免疫相关通路总体上调;差异最显著的基因包括上调的CXCL1(log2倍数变化4.98,校正后p<0.001)和CXCL6(4.43,p=0.016),以及下调的MME(-4.33,p约为0.001)。应答者的CD8细胞与调节性T细胞比值明显升高,而调节性T细胞占TIL(肿瘤浸润淋巴细胞)的相对比例降低。初步结果提示CXCL1和CXCL6可能成为具有治疗相关意义的候选生物标志物,有望帮助在专家共识之外进一步筛选适合接受TACE的HCC患者。
Distinct immune patterns of hepatocellular carcinoma (HCC) may have prognostic implications in the response to transarterial chemoembolization (TACE).
Thus, we aimed to exploratively analyze tumor tissue of HCC patients who do or do not respond to TACE, and to identify novel prognostic biomarkers predictive of response to TACE.
We retrospectively included 15 HCC patients who had three consecutive TACE between January 2019 and November 2019. Eight patients had a response while seven patients had no response to TACE. All patients had measurable disease according to mRECIST. Corresponding tumor tissue samples were processed for differential expression profiling using NanoString nCounter PanCancer immune profiling panel.
Immune-related pathways were broadly upregulated in TACE responders. The top differentially regulated genes were the upregulated CXCL1 (log2fc 4. 98, Benjamini-Hochberg (BH)- p < 0. 001), CXCL6 (log2fc 4. 43, BH- p = 0. 016) and the downregulated MME (log2fc -4. 33, BH- p 0. 001). CD8/T-regs was highly increased in responders, whereas the relative number of T-regs to tumor-infiltrating lymphocytes (TIL) was highly decreased.
We preliminary identified CXCL1 and CXCL6 as candidate genes that might have the potential to serve as therapeutically relevant biomarkers in HCC patients. This might pave the way to improve patient selection for TACE in HCC patients beyond expert consensus.
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