Monitoring Pre- and Post-Operative Immune Alterations in Patients With Locoregional Colorectal Cancer Who Underwent Laparoscopy by Single-Cell Mass Cytometry.
Monitoring Pre- and Post-Operative Immune Alterations in Patients With Locoregional Colorectal Cancer Who Underwent Laparoscopy by Single-Cell Mass Cytometry.
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通过单细胞质谱流式细胞术监测接受腹腔镜检查的局部结直肠癌患者术前和术后免疫变化
DOI：
10.3389/fimmu.2022.807539
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发表时间：
2022
影响因子：
7.3
通讯作者：
Su X
中科院分区：
文献类型：
--
作者：
Zhou C;Wang Z;Jiang B;Di J;Su X
手术切除是目前治疗局部结直肠癌的主要方法。然而，手术创伤导致控制性组织损伤，引起宿主免疫力的深刻改变，进而影响术后结果。CRC中手术诱导的免疫改变仍然定义不清。在这里，单细胞质量流式细胞术应用于术前收集的系列血液样本，并在术后第1天，第3天和第7天从24例接受腹腔镜手术切除CRC的患者中全面监测围手术期免疫细胞表型的改变和免疫反应的动态。免疫细胞亚群的表征显示，术后免疫应答是广泛的，但主要是抑制性的，这得到循环T细胞和自然杀伤（NK）细胞的总频率降低以及循环单核细胞上HLA-DR表达降低的支持。术后第1天T细胞比例明显下降，术后第3天恢复至术前水平。单核细胞的频率在术后第1天显著升高，并在第3天下降至基线水平。NK细胞在术后第3天暂时收缩。将T细胞、单核细胞、DC、NK细胞和B细胞分配成表型不同的单细胞簇。单细胞团的动态与整体谱系的动态不同。围手术期同一反应期的T细胞群波动不一致。与基线水平相比，CD 11b（+）CD 33（+）CD 14（+）CD 16（-）经典型单核细胞先扩张后收缩，而CD 11b（+）CD 33（+）CD 14（高）CD 16（低）中间型单核细胞的频率保持不变，单核细胞HLA-DR表达显著降低，中间型CD 56（亮）CD 16（+）NK细胞亚群的频率增加，CD 16（+）NK细胞亚群的频率降低。记忆性B淋巴细胞百分比术后升高。术后促炎细胞因子和抗炎细胞因子均发生改变。此外，一些细胞亚群的围手术期免疫扰动在手术后7天内未恢复。时序监测主要免疫谱系提供了手术引起的改变的概述，包括细胞扩增和收缩以及先天和适应性隔室中免疫细胞分布的精确定时变化，为肿瘤切除和免疫调节之间的相互作用提供了证据。
Surgical excision is currently the principal therapy for locoregional colorectal cancer (CRC). However, surgical trauma leads to controlled tissue damage, causing profound alterations in host immunity and, in turn, affecting post-operative outcomes. Surgery-induced immune alterations in CRC remain poorly defined. Here, single-cell mass cytometry was applied to serial blood samples collected pre-operatively, and on days 1, 3, and 7 post-operatively from 24 patients who underwent laparoscopic surgical resection of CRC to comprehensively monitor the perioperative phenotypic alterations in immune cells and dynamics of immune response. Characterization of immune cell subsets revealed that the post-operative immune response is broad but predominantly suppressive, supported by the decreases in total frequencies of circulating T cells and natural killer (NK) cells, as well as decreased HLA-DR expression on circulating monocytes. The proportion of T cells significantly decreased on day 1 and recovered to the pre-surgical level on day 3 after surgery. The frequency of monocytes was significantly elevated on day 1 after surgery and declined to baseline level on day 3. NK cells temporarily contracted on post-operative day 3. T cells, monocytes, DCs, NK cells, and B cells were partitioned into phenotypically different single-cell clusters. The dynamics of single-cell clusters were different from those of the bulk lineages. T cell clusters in the same response phase fluctuate inconsistently during the perioperative period. Comparing to the baseline levels, the frequencies of CD11b(+)CD33(+)CD14(+)CD16(−) classical monocytes expanded followed by contraction, whereas CD11b(+)CD33(+)CD14(high)CD16(low) intermediate monocytes remained unchanged; HLA-DR expression in monocytes were significantly reduced; the frequencies of intermediate CD56(bright)CD16(+) NK cell subsets increased; and the percentage of memory B lymphocytes were elevated after surgery. Post-operative pro- and anti-inflammatory cytokines were both altered. Furthermore, perioperative immune perturbations in some of the cell subsets were unrecovered within seven days after surgery. Chronological monitoring major immune lineages provided an overview of surgery-caused alterations, including cell augments and contractions and precisely timed changes in immune cell distribution in both innate and adaptive compartments, providing evidence for the interaction between tumor resection and immune modulation.