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

Abstract

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. 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. 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/mm2 ) pre-operatively to 7.6 ± 1.511 (cells/mm2 ) post-operatively (p < .0001). CD4+ cells turned from 7.270 ± 3.421 (cells/mm2 ) at T0 to 4.815 ± 1.511 cells/mm2 at T1 (p = .0173). CD8 expression values decreased from 4.360 ± 3.421 (cells/mm2 ) to 2.753 ± 1.451 (cell/mm2 ) at T1 (p = .0003). Monocyte/macrophage marker CD68 varied from 8.208 ± 2.314 (cells/mm2 ) at T0 to 7.600 ± 1876 (cells/mm2 ) at T1 (p = .0003). 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.