The immune microenvironment of regenerated lymph nodes treated with VEGF-C
10.3760/cma.j.cn114453-20190515-00160
- VernacularTitle:血管内皮生长因子-C对裸小鼠再生淋巴结免疫微环境的影响
- Author:
Lei CUI
1
;
Zheng YANG
;
Na LIN
;
Chen YANG
;
Wenfang DONG
;
Qinhao GU
;
Yanjun FENG
;
Ye ZHANG
;
Leren HE
Author Information
1. 中国医学科学院北京协和医学院整形外科医院整形七科 100144
- Keywords:
Autologous lymph nodes fragmentary transplantation;
Vascular endothelial growth factor-C;
Lymph node microenvironment;
Suppressive immune response
- From:
Chinese Journal of Plastic Surgery
2020;36(6):672-678
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the microenvironment associated with tumorimmunity in regenerated lymph nodes treated with VEGF-C, which involves the lymphangiogenesis, chemokine as well as alteration of cell populations.Methods:A total of 10 nude mice were randomized to 2 groups. 5 mice in group A were treated with autologous lymph nodes fragmentary transplantation together with VEGF-C, 5 mice without any intervention in group B were served as control group. 4 weeks after surgeries, MDA-MB-231-Luc-GFP cells (5×10 6 cells/mouse, 100 μl of 40% matrigel solution) were injected subcutaneously in the thoracic flunk of nude mice in group A, the same number cells were implanted into the second mammary fat pad in group B as well. 4 weeks post inoculation, the tumor draining lymph nodes (TDLNs) in both groups were harvested, and the microenvironment was assessed by hematoxylin-eosin (HE) staining and multispectral immunofluorescence staining for LYVE-1, chemokine CCL21, programmed death ligand-1(PD-L1) and F4/80. Results:The specific markers were analyzed based on positive cell percentage between group A and group B. The LYVE-1 and F4/80 expression in the group A was significantly higher than that in group B[LYVE-1: group A 21.44 0(34.675)% vs group B 2.964 (4.160)%, P<0.001; F4/80: group A 5.396 (7.205)% vs group B 3.573 (2.670)%, P=0.020)], and there were no significant differences in the expression of CCL21 and PD-L1 between these two groups [CCL21: group A 21.470((29.145)% vs group B 16.430((29.145)%( P=0.166); PD-L1: group A10.000 (14.430)%vs group B 4.070 (26.740)%, P=0.091]. Additionally, the double positive expression of LYVE-1/CCL21 and LYVE-1/F4/80 had still statistically significant differences[LYVE-1/CCL21: group A 8.637 (13.150)% vs group B 1.571 (1.680)%, P<0.001; LYVE-1/F4/80: group A 6.181 (9.050)% vs group B 1.454 (0.830)%, P<0.001], whereas, the two groups did not differ from each other in the double positive expression of LYVE-1/PD-L1 [group A 3.617 (4.195)% vs group B 2.363 (3.900)%, P=0.266]. Conclusions:The renewed lymph nodes treated with VEGF-C demonstrate some more immune suppressive conditions such as lymphatic endothelial cells hyperplasia, myeloid-derived suppressor cells infiltration, enhanced expression of CCL21 and PD-L1.
