PMID- 33278092
OWN - NLM
STAT- MEDLINE
DCOM- 20210514
LR  - 20231110
IS  - 2542-5641 (Electronic)
IS  - 0366-6999 (Print)
IS  - 0366-6999 (Linking)
VI  - 134
IP  - 3
DP  - 2020 Dec 3
TI  - Targeted inhibition of myeloid-derived suppressor cells in the tumor 
      microenvironment by low-dose doxorubicin to improve immune efficacy in murine 
      neuroblastoma.
PG  - 334-343
LID - 10.1097/CM9.0000000000001234 [doi]
AB  - BACKGROUND: High agglomeration of myeloid-derived suppressor cells (MDSCs) in 
      neuroblastoma (NB) impeded therapeutic effects. This study aimed to investigate 
      the role and mechanism of targeted inhibition of MDSCs by low-dose doxorubicin 
      (DOX) to enhance immune efficacy in NB. METHODS: Bagg albino (BALB/c) mice were 
      used as tumor-bearing mouse models by injecting Neuro-2a cells, and MDSCs were 
      eliminated by DOX or dopamine (DA) administration. Tumor-bearing mice were 
      randomly divided into 2.5 mg/kg DOX, 5.0 mg/kg DOX, 50.0 mg/kg DA, and control 
      groups (n = 20). The optimal drug and its concentration for MDSC inhibition were 
      selected according to tumor inhibition. NB antigen-specific cytotoxic T cells 
      (CTLs) were prepared. Tumor-bearing mice were randomly divided into DOX, CTL, 
      anti-ganglioside (GD2), DOX+CTL, DOX+anti-GD2, and control groups. Following 
      low-dose DOX administration, immunotherapy was applied. The levels of human 
      leukocyte antigen (HLA)-I, CD8, interleukin (IL)-2 and interferon (IFN)-gamma in 
      peripheral blood, CTLs, T-helper 1 (Thl)/Th2 cytokines, perforin, granzyme and 
      tumor growth were compared among the groups. The Wilcoxon two-sample test and 
      repeated-measures analysis of variance were used to analyze results. RESULTS: The 
      slowest tumor growth (F = 6.095, P = 0.018) and strongest MDSC inhibition 
      (F = 14.632, P = 0.001) were observed in 2.5 mg/kg DOX group. Proliferation of T 
      cells was increased (F = 448.721, P < 0.001) and then decreased (F = 2.047, 
      P = 0.186). After low-dose DOX administration, HLA-I (F = 222.489), CD8 
      (F = 271.686), Thl/Th2 cytokines, CD4+ and CD8+ lymphocytes, granzyme 
      (F = 2376.475) and perforin (F = 488.531) in tumor, IL-2 (F = 62.951) and IFN-gamma 
      (F = 240.709) in peripheral blood of each immunotherapy group were all higher 
      compared with the control group (all of P values < 0.05). The most significant 
      increases in the aforementioned indexes and the most notable tumor growth 
      inhibition were observed in DOX+anti-GD2 and DOX+CTL groups. CONCLUSIONS: 
      Low-dose DOX can be used as a potent immunomodulatory agent that selectively 
      impairs MDSC-induced immunosuppression, thereby fostering immune efficacy in NB.
CI  - Copyright (c) 2021 The Chinese Medical Association, produced by Wolters Kluwer, 
      Inc. under the CC-BY-NC-ND license.
FAU - Xu, Wei-Li
AU  - Xu WL
AD  - Department of Pediatric Surgery, The Second Hospital of Hebei Medical University, 
      Shijiazhuang, Hebei 050000, China.
FAU - Shi, Bao-Jun
AU  - Shi BJ
AD  - Department of Pediatric Surgery, The Second Hospital of Hebei Medical University, 
      Shijiazhuang, Hebei 050000, China.
FAU - Li, Suo-Lin
AU  - Li SL
AD  - Department of Pediatric Surgery, The Second Hospital of Hebei Medical University, 
      Shijiazhuang, Hebei 050000, China.
FAU - Yu, Feng-Xue
AU  - Yu FX
AD  - Department of Central Laboratory, The Second Hospital of Hebei Medical 
      University, Shijiazhuang, Hebei 050000, China.
FAU - Guo, Li-Na
AU  - Guo LN
AD  - Department of Central Laboratory, The Second Hospital of Hebei Medical 
      University, Shijiazhuang, Hebei 050000, China.
FAU - Li, Meng
AU  - Li M
AD  - Department of Pediatric Surgery, The Second Hospital of Hebei Medical University, 
      Shijiazhuang, Hebei 050000, China.
FAU - Hu, Zhi-Gang
AU  - Hu ZG
AD  - Department of General Surgery, The Second Hospital of Hebei Medical University, 
      Shijiazhuang, Hebei 050000, China.
FAU - Li, Gui-Xin
AU  - Li GX
AD  - Department of General Surgery, The Second Hospital of Hebei Medical University, 
      Shijiazhuang, Hebei 050000, China.
FAU - Zhou, Hui
AU  - Zhou H
AD  - Department of Pediatric Surgery, The Second Hospital of Hebei Medical University, 
      Shijiazhuang, Hebei 050000, China.
LA  - eng
PT  - Journal Article
DEP - 20201203
PL  - China
TA  - Chin Med J (Engl)
JT  - Chinese medical journal
JID - 7513795
RN  - 80168379AG (Doxorubicin)
SB  - IM
MH  - Animals
MH  - Doxorubicin/therapeutic use
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - *Myeloid-Derived Suppressor Cells
MH  - *Neuroblastoma/drug therapy
MH  - Tumor Microenvironment
PMC - PMC7846436
COIS- None.
EDAT- 2020/12/06 06:00
MHDA- 2021/05/15 06:00
PMCR- 2021/02/05
CRDT- 2020/12/05 17:06
PHST- 2020/12/06 06:00 [pubmed]
PHST- 2021/05/15 06:00 [medline]
PHST- 2020/12/05 17:06 [entrez]
PHST- 2021/02/05 00:00 [pmc-release]
AID - 00029330-202102050-00011 [pii]
AID - CMJ-2020-2029 [pii]
AID - 10.1097/CM9.0000000000001234 [doi]
PST - epublish
SO  - Chin Med J (Engl). 2020 Dec 3;134(3):334-343. doi: 10.1097/CM9.0000000000001234.