PMID- 32676336
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220415
IS  - 2218-6751 (Print)
IS  - 2226-4477 (Electronic)
IS  - 2218-6751 (Linking)
VI  - 9
IP  - 3
DP  - 2020 Jun
TI  - The effect of combining Endostar with radiotherapy on blood vessels, 
      tumor-associated macrophages, and T cells in brain metastases of Lewis lung 
      cancer.
PG  - 745-760
LID - 10.21037/tlcr-20-500 [doi]
AB  - BACKGROUND: Combining Endostar (ES) with radiotherapy (RT) has shown a promising 
      therapeutic effect on non-small cell lung carcinoma with brain metastases (BMs) 
      in clinical practice. However, the specific mechanism is not yet fully 
      understood. The present study aimed to investigate the effects of ES on blood 
      vessels, tumor-associated macrophages (TAMs), and T cells in a tumor 
      microenvironment treated with RT. METHODS: BM models were established by 
      stereotactic and intracarotid injection of luciferase-Lewis lung cancer (LLC) 
      cells into female C57BL mice. The animals were randomly divided into 4 groups: 
      normal saline (NS), ES, RT, and ES plus radiotherapy (ES + RT) groups. Tumor size 
      was determined with the IVIS imaging system. Tumor specimens were stained with 
      CD34 and alpha-SMA to investigate tumor vascular changes. The proportions of TAMs, 
      CD4(+) T cells, and CD8(+) T cells in tumor tissues were determined by flow 
      cytometry and immunofluorescence. The expressions of hypoxia-inducible factor 1alpha 
      (HIF-1alpha) and CXCR4 were deduced using western blotting and immunohistochemistry 
      (IHC). RESULTS: ES + RT significantly suppressed tumor growth compared to the 
      other 3 groups. RT decreased M1 and increased M2 in microglial cells and bone 
      marrow-derived macrophages (BMDMs) relative to NS, while ES had the opposite 
      effect. The ratio of CD8(+)T/CD4(+)T was increased in the ES + RT group compared 
      to the other 3 groups. Tumor vascular maturity (alpha-SMA(+)/CD34(+)) was increased 
      while HIF-1alpha was significantly suppressed in the ES + RT group. CXCR4 expression, 
      which is involved in TAM recruitment, increased following RT, whereas, ES 
      attenuated its expression. CONCLUSIONS: Our findings suggest that ES can promote 
      the normalization of tumor blood vessels and increase the anti-tumor 
      immune-related immune cells infiltrating the tumor following RT treatment.
CI  - 2020 Translational Lung Cancer Research. All rights reserved.
FAU - Peng, Ling
AU  - Peng L
AD  - Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of 
      Science and Technology, Wuhan 430022, China.
FAU - Wang, Ying
AU  - Wang Y
AD  - Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of 
      Science and Technology, Wuhan 430022, China.
FAU - Fei, Shihong
AU  - Fei S
AD  - Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of 
      Science and Technology, Wuhan 430022, China.
FAU - Wei, Chunhua
AU  - Wei C
AD  - Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of 
      Science and Technology, Wuhan 430022, China.
FAU - Tong, Fan
AU  - Tong F
AD  - Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of 
      Science and Technology, Wuhan 430022, China.
FAU - Wu, Gang
AU  - Wu G
AD  - Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of 
      Science and Technology, Wuhan 430022, China.
FAU - Ma, Hong
AU  - Ma H
AD  - Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of 
      Science and Technology, Wuhan 430022, China.
FAU - Dong, Xiaorong
AU  - Dong X
AD  - Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of 
      Science and Technology, Wuhan 430022, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Transl Lung Cancer Res
JT  - Translational lung cancer research
JID - 101646875
PMC - PMC7354151
OTO - NOTNLM
OT  - Endostar (ES)
OT  - Lung cancer
OT  - brain metastases (BMs)
OT  - radiotherapy (RT)
OT  - tumor-associated macrophages (TAMs)
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at http://dx.doi.org/10.21037/tlcr-20-500). The authors have no 
      conflicts of interest to declare.
EDAT- 2020/07/18 06:00
MHDA- 2020/07/18 06:01
PMCR- 2020/06/01
CRDT- 2020/07/18 06:00
PHST- 2020/07/18 06:00 [entrez]
PHST- 2020/07/18 06:00 [pubmed]
PHST- 2020/07/18 06:01 [medline]
PHST- 2020/06/01 00:00 [pmc-release]
AID - tlcr-09-03-745 [pii]
AID - 10.21037/tlcr-20-500 [doi]
PST - ppublish
SO  - Transl Lung Cancer Res. 2020 Jun;9(3):745-760. doi: 10.21037/tlcr-20-500.