Department of Biochemistry and Immunology, Vejle Hospital - University Hospital of Southern Denmark, Vejle, Denmark; Danish Colorectal Cancer Center South, Vejle Hospital - University Hospital of Southern Denmark, Vejle, Denmark.
Danish Colorectal Cancer Center South, Vejle Hospital - University Hospital of Southern Denmark, Vejle, Denmark; Department of Oncology, Vejle Hospital - University Hospital of Southern Denmark, Vejle, Denmark.
Clin Colorectal Cancer. 2024 Dec;23(4):372-381.e1. doi: 10.1016/j.clcc.2024.05.012. Epub 2024 Jun 18.
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 IFNγ as a surrogate marker of NKA. Normal NKA was defined as IFNγ > 250 pg/mL and low NKA was defined as IFNγ < 250 pg/mL.
The CRC cohort was classified into either PREOP having preoperative low NKA or PREOP having preoperative normal NKA. The median NKA of the PREOP subset was only in the normal range in the POD3 months sample, whereas median NKA of the PREOP subset and the VH cohort were only low in the POD1 sample. While PREOP differed from VH in the PREOP-, POD1-, and POD3-6 samples (P =.0006, P = .0181, and P = .0021), NKA in PREOP 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.
手术创伤会导致免疫功能受损,但目前尚不清楚癌症和良性疾病的手术是否会引起相当程度的免疫抑制。在这里,我们比较了腹腔镜手术对结直肠癌(CRC)和腹疝(VH)患者免疫生物标志物的影响。
在术前(PREOP)和术后第 1、3-6、2 周和 3 个月时,从 CRC(n = 29)和 VH(n = 9)患者的血液样本中测量自然杀伤细胞活性(NKA)、白细胞亚群和可溶性程序性死亡配体 1(sPD-L1)。通过使用 IFNγ作为 NKA替代标志物的 NK Vue 测定法评估 NKA。正常 NKA 定义为 IFNγ>250 pg/mL,低 NKA 定义为 IFNγ<250 pg/mL。
CRC 队列分为 PREOP 术前低 NKA 或 PREOP 术前正常 NKA。PREOP 亚组的中位 NKA 仅在 POD3 个月样本中处于正常范围,而 PREOP 亚组和 VH 队列的中位 NKA 仅在 POD1 样本中较低。尽管 PREOP 在 PREOP-、POD1-和 POD3-6 样本中与 VH 不同(P =.0006,P =.0181,P =.0021),但 PREOP 和 VH 中 NKA 在 POD1 样本中有所不同(P =.0226)。两个队列在围手术期白细胞亚群的分布上没有明显差异。
PREOP 时 NKA 正常的 CRC 患者和 VH 患者的 NKA 恢复模式相同,而 PREOP 时 NKA 较低的 CRC 亚组似乎经历了 NK 细胞功能障碍的延长。由于低 NKA 与复发有关,PREOP 时的 NKA 水平可能可以识别出在围手术期受益于免疫增强治疗的患者。