RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:M1 macrophage predicted efficacy of neoadjuvant camrelizumab combined with chemotherapy vs chemotherapy alone for locally advanced ESCC: A pilot study.
M1 macrophage predicted efficacy of neoadjuvant camrelizumab combined with chemotherapy vs chemotherapy alone for locally advanced ESCC: A pilot study.
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新辅助卡瑞利珠单抗联合化疗提高了局部晚期 ESCC 的 ORR。M1 型肿瘤相关巨噬细胞和 CD56dim NK 细胞可能可用于预测卡瑞利珠单抗的疗效。
免疫治疗在消化道相关肿瘤中的疗效和安全性已得到广泛认可。然而,新辅助卡瑞利珠单抗治疗局部晚期食管鳞状细胞癌(ESCC)的疗效尚未确定。本研究比较了卡瑞利珠单抗联合新辅助DCF(多西他赛、顺铂和氟尿嘧啶)方案与单纯DCF方案治疗ESCC的疗效,并探索与ESCC免疫治疗反应免疫浸润相关的生物标志物。
我们入组并随机分配II-IVa期ESCC患者接受两种研究治疗:卡瑞利珠单抗联合多西他赛、顺铂和氟尿嘧啶(DCF)方案以及单独DCF方案。在新辅助治疗前后获取用于多重免疫荧光(mIF)的组织。采用实体瘤疗效评价标准RECIST 1.1版(RECIST 1.1)和肿瘤消退分级(TRG)评估疗效。
共纳入30例患者。接受新辅助卡瑞利珠单抗治疗后,客观缓解率(ORR)和疾病控制率(DCR)分别为46.7%(7/15)和95.7%(14/15)。无患者报告完全缓解,而化疗组的ORR和DCR分别为26.7%(4/15)和86.7%(13/15)。联合组15例患者中有3例在新辅助治疗后实现R0切除,化疗组所有患者(15/15)均实现R0切除。在联合组中,应答者的M1型肿瘤相关巨噬细胞和CD56dim NK细胞比非应答者更丰富(p < 0.05)。应答者中观察到更高的M1/M2比值(p < 0.05)。在NGS方面,拷贝数扩增基因中,11q13扩增子(CCND1/FGF19/FGF4/FGF3)出现频率最高(47%,7/15)。
We enrolled and randomly assigned patients with stage II-IVa ESCC to two study treatments: camrelizumab combined with docetaxel, cisplatin and fluorouracil (DCF) regimen and DCF regimen alone. The tissue for multiplex immunofluorescence (mIF) was obtained before and after neoadjuvant therapy. The Response Evaluation Criteria in Solid Tumors RECIST Version 1.1 (RECIST 1.1) and Tumor Regression Grade (TRG) was used to evaluate efficacy.
A total of 30 patients were enrolled in the study. Following neoadjuvant camrelizumab, the objective response rate (ORR) and the disease control rate (DCR) were 46.7% (7/15) and 95.7% (14/15), respectively. No patients reported complete remission, while ORR and DCR in the chemotherapy group were 26.7% (4/15) and 86.7% (13/15), respectively. R0 resection after neoadjuvant treatment was achieved in 3 out of 15 patients in the combined group and in all patients (15/15) in the chemotherapy group. In the combined group, M1-type tumor-associated macrophages and CD56dim NK cells were more abundant in responders than in non-responders (p < 0.05). A higher M1/M2 ratio was observed in responders (p < 0.05). With respect to the NGS, among the copy number amplified genes, the 11q13 amplicon (CCND1/FGF19/FGF4/FGF3) showed the highest frequency (47%, 7/15).
Neoadjuvant camrelizumab combined with chemotherapy improved ORR in locally advanced ESCC. M1-type tumor-associated macrophages and CD56dim NK cells might be utilized to predict camrelizumab efficacy.
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