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淋巴结转移对免疫调节的评估:淋巴水肿患者的初步组织学证据。

Evaluation of modulation of immunity by lymph node transfer: A preliminary histological evidence in lymphedema patients.

机构信息

Division of Plastic and Reconstructive Surgery, Department of Precision and Regenerative Medicine and Jonic Area, University of Bari, Bari, Italy.

Department of Plastic Surgery, China Medical University Hospital, Taichung, Taiwan.

出版信息

Microsurgery. 2024 Jan;44(1):e31123. doi: 10.1002/micr.31123. Epub 2023 Oct 3.

DOI:10.1002/micr.31123
PMID:37788091
Abstract

BACKGROUND

The exact knowledge of the local biological and immunological effects of vascularized lymph node transfer (VLNT) continues to be an emerging science but a positive control positive control over infectious and immune-mediated processes is often advocated. Knowing the characterization of the inflammatory infiltrate associated with lymphedema, the aim of this paper is to verify the hypothesis that VLNT is able to modulate the inflammatory and immune microenvironment of lymphedematous tissue by evaluating any modification of the local inflammatory cell infiltrate.

PATIENTS AND METHODS

A prospectively database of patients who received VLN transfer for lower extremity lymphedema between January 2018 and December 2020 was reviewed. Nine patients diagnosed with extremities' stage II secondary lymphedema were included, with a mean age of 55.3 (range 39-66 years) years. Gastroepiploic lymph node transfer was performed in all patients and transferred heterotopically. Full thickness 6-mm skin punch biopsies were obtained from all voluntary lymph node transfer patients at identical sites of the lymphedematous limb during the surgical procedure of VLNT (T0) and 1 year later (T1). Immunohistochemistry was performed using antibodies against the following markers: anti-CD3; anti-CD4; anti-CD8; anti-CD68. Data at T0 were compared to those at T1.

RESULTS

Post-operative course was uneventful in all cases experiencing a significant reduction (almost a third) in terms of cellulitis episodes: The median duration of follow-up for patients was 28.3 months (range 12-40). The analysis of the density of the inflammatory cells as a whole revealed a significant reduction at T1 compared to T0. Specifically, CD3 expression levels turned from 16.36 ± 3.421 (cells/mm ) pre-operatively to 7.6 ± 1.511 (cells/mm ) post-operatively (p < .0001). CD4+ cells turned from 7.270 ± 3.421 (cells/mm ) at T0 to 4.815 ± 1.511 cells/mm at T1 (p = .0173). CD8 expression values decreased from 4.360 ± 3.421 (cells/mm ) to 2.753 ± 1.451 (cell/mm ) at T1 (p = .0003). Monocyte/macrophage marker CD68 varied from 8.208 ± 2.314 (cells/mm ) at T0 to 7.600 ± 1876 (cells/mm ) at T1 (p = .0003).

CONCLUSION

VLNT decreases skin and subcutaneous tissues' infiltration of inflammatory cells, providing one explanation for the positive control of lymph node transfer procedure over infectious and immune-mediated processes.

摘要

背景

血管化淋巴结转移 (VLNT) 的局部生物学和免疫学效应的准确知识仍然是一个新兴科学,但通常提倡使用感染和免疫介导过程的阳性对照。了解与淋巴水肿相关的炎症浸润的特征,本文旨在通过评估局部炎症细胞浸润的任何变化来验证 VLNT 能够调节淋巴水肿组织的炎症和免疫微环境的假设。

患者和方法

回顾了 2018 年 1 月至 2020 年 12 月期间因下肢淋巴水肿接受 VLN 转移的患者的前瞻性数据库。纳入了 9 名诊断为下肢二级继发性淋巴水肿的患者,平均年龄为 55.3(39-66 岁)岁。所有患者均行胃网膜淋巴结转移,并异位转移。在 VLNT(T0)手术过程中,所有自愿接受淋巴结转移的患者均在淋巴水肿肢体的相同部位获取全厚 6mm 皮肤穿刺活检,以及 1 年后(T1)。使用针对以下标记物的抗体进行免疫组织化学染色:抗-CD3;抗-CD4;抗-CD8;抗-CD68。将 T0 时的数据与 T1 时的数据进行比较。

结果

所有病例的术后过程均无并发症,均经历了细胞性水肿发作次数的显著减少(几乎减少了三分之一):患者的中位随访时间为 28.3 个月(范围 12-40)。整体炎症细胞密度分析显示,T1 时与 T0 相比显著降低。具体而言,CD3 表达水平从术前的 16.36±3.421(细胞/mm )降至术后的 7.6±1.511(细胞/mm )(p<0.0001)。CD4+细胞从 T0 时的 7.270±3.421(细胞/mm )降至 T1 时的 4.815±1.511 细胞/mm (p=0.0173)。CD8 表达值从 4.360±3.421(细胞/mm )降至 T1 时的 2.753±1.451(细胞/mm )(p=0.0003)。单核细胞/巨噬细胞标志物 CD68 从 T0 时的 8.208±2.314(细胞/mm )降至 T1 时的 7.600±1876(细胞/mm )(p=0.0003)。

结论

VLNT 减少皮肤和皮下组织的炎症细胞浸润,为淋巴结转移过程对感染和免疫介导过程的阳性控制提供了一种解释。

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