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:A Comparison of Cellular Immune Response and Immunological Biomarkers in Laparoscopic Surgery for Colorectal Cancer and Benign Disorders.
A Comparison of Cellular Immune Response and Immunological Biomarkers in Laparoscopic Surgery for Colorectal Cancer and Benign Disorders.
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术前 NKA 正常且 VH 的 CRC 患者表现出与 NKA 相同的恢复模式,而术前 NKA 低的 CRC 亚组似乎经历了延长的 NK 细胞损伤。由于低 NKA 与复发相关,术前 NKA 水平可能识别出围手术期将从免疫增强治疗中获益的患者。
手术创伤会导致免疫损伤,但癌症手术与良性疾病手术是否引发相当程度的免疫抑制,目前尚不清楚。在此,我们比较了腹腔镜手术对结直肠癌(CRC)患者和腹壁疝(VH)患者免疫生物标志物的影响。
从CRC(n = 29)和VH(n = 9)患者术前(PREOP)及术后第(POD)1天、3-6天、2周和3个月采集的血样中检测NK 细胞活性(NKA)、白细胞亚群和可溶性程序性死亡配体1(sPD-L1)。NKA通过NK Vue检测法评估,该方法使用IFN水平作为NKA的替代标志物。正常NKA定义为IFN > 250 pg/mL,低NKA定义为IFN < 250 pg/mL。
CRC队列被分为PREOP LOW(术前NKA低)或PREOP HIGH(术前NKA正常)。PREOP LOW亚组的中位NKA仅在POD3个月样本中处于正常范围,而PREOP HIGH亚组和VH队列的中位NKA仅在POD1样本中偏低。虽然PREOP LOW在PREOP-、POD1-和POD3-6样本中与VH不同(P =.0006、P = .0181和P = .0021),但PREOP HIGH和VH中的NKA在POD1样本中存在差异(P = .0226)。各队列在围手术期白细胞亚群的分布上没有明显差异。
Surgical trauma causes immune impairment, but it is largely unknown whether surgery for cancer and benign diseases instigate comparable levels of immune inhibition. Here, we compared the impact of laparoscopic surgery on immunological biomarkers in patients with colorectal cancer (CRC) and ventral hernia (VH).
Natural Killer cell activity (NKA), leukocyte subsets, and soluble programmed death ligand 1 (sPD-L1) were measured in blood samples collected from CRC (n = 29) and VH (n = 9) patients preoperatively (PREOP) and on postoperative day (POD) 1, 3-6, 2 weeks and 3 months. NKA was evaluated by the NK Vue assay that uses the level of IFN as a surrogate marker of NKA. Normal NKA was defined as IFN > 250 pg/mL and low NKA was defined as IFN < 250 pg/mL.
The CRC cohort was classified into either PREOP LOW having preoperative low NKA or PREOP HIGH having preoperative normal NKA. The median NKA of the PREOP LOW subset was only in the normal range in the POD3 months sample, whereas median NKA of the PREOP HIGH subset and the VH cohort were only low in the POD1 sample. While PREOP LOW differed from VH in the PREOP-, POD1-, and POD3-6 samples (P =.0006, P = .0181, and P = .0021), NKA in PREOP HIGH and VH differed in the POD1 samples (P = .0226). There were no apparent differences in the distribution of leukocyte subsets in the perioperative period between the cohorts.
CRC patients with preoperative normal NKA and VH patients showed the same pattern of recovery in NKA, while the CRC subset with preoperative low NKA seemed to experience prolonged NK cell impairment. As low NKA is associated with recurrence, preoperative level of NKA may identify patients who will benefit from immune-enhancing therapy in the perioperative period.
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