PMID- 33493800
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231110
IS  - 1936-5233 (Print)
IS  - 1936-5233 (Electronic)
IS  - 1936-5233 (Linking)
VI  - 14
IP  - 4
DP  - 2021 Apr
TI  - Absent in melanoma 2-mediating M1 macrophages facilitate tumor rejection in renal 
      carcinoma.
PG  - 101018
LID - S1936-5233(21)00010-3 [pii]
LID - 10.1016/j.tranon.2021.101018 [doi]
LID - 101018
AB  - Absent in melanoma 2 (AIM2) as an immune regulator for the regulation of 
      tumor-associated macrophages (TAMs) function is unclear in tumor development. 
      Here, the AIM2 function was investigated in TAMs-mediated malignant behaviors of 
      renal carcinoma. The correlation analysis result showed that the AIM2 expression 
      in TAMs was negatively correlated with the percentages of M2-like polarization 
      phenotype in human or murine renal cancer specimens. By the cocultured assay with 
      bone marrow-derived macrophages (BMDMs) and Renca cells, overexpression of AIM2 
      in macrophages enhanced the inflammasome activation and reversed the phenotype 
      from M2 to M1. Compared with BMDMs-Ctrl cocultured group, BMDMs-AIM2 cocultured 
      group showed reduced tumor cell proliferation and migration. The blockade of 
      inflammasome activation by the inhibitor Ac-YVAD-CMK abrogated AIM2-mediated M1 
      polarization and the inhibition of tumor cell growth. To evaluate the therapeutic 
      efficacy of AIM2-mediated M1 macrophages in vivo, BMDMs-AIM2 were intravenously 
      injected into subcutaneous Renca-tumor mice. The results showed that the 
      infiltration of M1 TAMs was increased and tumor growth was suppressed in 
      BMDMs-AIM2-treated mice when compared with BMDMs-Ctrl-treat mice. Accordingly, 
      the blockade of inflammasome activation reduced the anti-tumor activities of 
      BMDMs-AIM2. Moreover, the lung metastases of renal carcinoma were suppressed by 
      the administration of BMDMs-AIM2 accompanied with the reduced tumor foci. These 
      results demonstrated that AIM2 enhanced TAMs polarization switch from 
      anti-inflammatory M2 phenotypy to pro-inflammatory M1 through inflammasome 
      signaling activation, thus exerting therapeutic intervention in renal carcinoma 
      models. Our results provide a possible molecular mechanism for the modulation of 
      TAMs polarization in tumor microenvironment and open a new potential therapeutic 
      approach for renal cancer.
CI  - Copyright (c) 2021. Published by Elsevier Inc.
FAU - Chai, Dafei
AU  - Chai D
AD  - Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China; 
      Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, 
      Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China. Electronic 
      address: chaidafei@xzhmu.edu.cn.
FAU - Zhang, Zichun
AU  - Zhang Z
AD  - Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China; 
      Department of Urology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 
      Jiangsu 221002, P.R. China.
FAU - Shi, Shang Yuchen
AU  - Shi SY
AD  - Department of Radiation Oncology, Affiliated Hospital of Xuzhou Medical 
      University, Xuzhou, Jiangsu 221002, P.R. China.
FAU - Qiu, Dong
AU  - Qiu D
AD  - Department of Urology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 
      Jiangsu 221002, P.R. China.
FAU - Zhang, Chen
AU  - Zhang C
AD  - Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China.
FAU - Wang, Gang
AU  - Wang G
AD  - Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China; 
      Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, 
      Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China.
FAU - Fang, Lin
AU  - Fang L
AD  - Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China; 
      Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, 
      Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China.
FAU - Li, Huizhong
AU  - Li H
AD  - Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China; 
      Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, 
      Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China.
FAU - Tian, Hui
AU  - Tian H
AD  - Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China; 
      Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, 
      Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China.
FAU - Li, Hailong
AU  - Li H
AD  - Department of Urology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 
      Jiangsu 221002, P.R. China.
FAU - Zheng, Junnian
AU  - Zheng J
AD  - Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China; 
      Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, 
      Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China. Electronic 
      address: jnzheng@xzhmu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20210122
PL  - United States
TA  - Transl Oncol
JT  - Translational oncology
JID - 101472619
PMC - PMC7823216
OTO - NOTNLM
OT  - AIM2
OT  - Inflammasome
OT  - Macrophage polarization
OT  - Renal carcinoma
OT  - TAMs
COIS- Declaration of Competing Interests The authors declare that they have no 
      competing interests.
EDAT- 2021/01/26 06:00
MHDA- 2021/01/26 06:01
PMCR- 2021/01/22
CRDT- 2021/01/25 20:13
PHST- 2020/11/04 00:00 [received]
PHST- 2021/01/06 00:00 [revised]
PHST- 2021/01/11 00:00 [accepted]
PHST- 2021/01/26 06:00 [pubmed]
PHST- 2021/01/26 06:01 [medline]
PHST- 2021/01/25 20:13 [entrez]
PHST- 2021/01/22 00:00 [pmc-release]
AID - S1936-5233(21)00010-3 [pii]
AID - 101018 [pii]
AID - 10.1016/j.tranon.2021.101018 [doi]
PST - ppublish
SO  - Transl Oncol. 2021 Apr;14(4):101018. doi: 10.1016/j.tranon.2021.101018. Epub 2021 
      Jan 22.