open access

https://hdl.handle.net/2115/94191

Sentinel node restoration by vascularized lymph node transfer in mice

英語

2024-01

John Wiley & Sons

Microsurgery

44(1)

e30981

Background Recent reports have indicated that vascularized lymph node transfer (VLNT) may improve the impaired immunity in lymphedema but there has been no report concerning anti-cancer immunity. In the early tumor immune response, dendritic cells (DCs) participate in tumor recognition and antigen presentation in local lymphatics. Here, we investigated the impact of VLNT on DC dynamics against cancer in mouse models. Methods Forty-seven 8-week-old C57BL/6 N male mice were divided into three surgical groups: a VLNT model in which a vascularized inguinal lymph node (LN) flap was transferred into the ipsilateral fossa after a popliteal LN was removed; a LN dissection (LND) model in which the popliteal LN was dissected; and a control model in which a skin incision was made at the popliteal fossa and an ipsilateral inguinal LN was removed. Postoperative lymphatic flows were observed by indocyanine green lymphography and B16-F10-luc2 mouse melanoma were implanted into the ipsilateral footpad. The proportion of DCs in the transplanted nodes was measured by CD11c immunohistochemistry using digital imaging analysis 4 days after cancer implantation. Metastases to the lungs and LNs were quantitatively evaluated by luciferase assay 4 weeks after cancer implantation. Results After VLNT, lymphatic reconnection was observed in 59.2% of mice. The proportion of DCs was significantly higher in the VLNT group with lymphatic reconnection (8.6% ± 1.0%) than in the naïve LN (4.3% ± 0.4%) (p < .001). The tumor burden of lung metastases was significantly less in the VLNT group with lymphatic reconnection compared with the LND group (p = .049). Conclusions Metastasis decreased in mice with reconnected lymphatics after VLNT. A possible explanation was that lymphatic restoration may have contributed to the tumor immune response by allowing DC migration to LNs.

学術雑誌論文

Accepted Manuscript

This is the peer reviewed version of the following article: Kusajima, E. G., Yamamoto, Y., Ishikawa, K., Miura, T., Funayama, E., Osawa, M., Takagi, R., & Maeda, T. (2024). Sentinel node restoration by vascularized lymph node transfer in mice. Microsurgery, 44(1), e30981., which has been published in final form at https://doi.org/10.1002/micr.30981. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.

0738-1085

1098-2752