PMID- 36654820
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230120
IS  - 2692-3114 (Electronic)
IS  - 2692-3114 (Linking)
VI  - 3
IP  - 6
DP  - 2022
TI  - Dendritic cell-targeting chemokines inhibit colorectal cancer progression.
PG  - 828-840
LID - 10.37349/etat.2022.00115 [doi]
AB  - AIM: Recent progress in cancer immunotherapy has shown its promise and prompted 
      researchers to develop novel therapeutic strategies. Dendritic cells (DCs) are 
      professional antigen-presenting cells crucial for initiating adaptive anti-tumor 
      immunity, therefore a promising target for cancer treatment. Here, anti-tumor 
      activities of DC-targeting chemokines were explored in murine colorectal tumor 
      models. METHODS: The correlation of chemokine messenger RNA (mRNA) expression 
      with DC markers was analyzed using The Cancer Genome Atlas (TCGA) dataset. Murine 
      colorectal tumor cell lines (CT26 and MC38) stably overexpressing mouse C-C motif 
      chemokine ligand 3 (CCL3), CCL19, CCL21, and X-C motif chemokine ligand 1 (XCL1) 
      were established by lentiviral transduction. The effect of chemokines on tumor 
      cell proliferation/survival was evaluated in vitro by cell counting kit-8 (CCK-8) 
      assay and colony formation assay. Syngeneic subcutaneous tumor models were used 
      to study the effects of these chemokines on tumor growth. Ki-67 expression in 
      tumors was examined by immunohistochemistry. Immune cells in the tumor 
      microenvironment (TME) and lymph nodes were analyzed by flow cytometry. RESULTS: 
      Expression of the four chemokines was positively correlated with the two DC 
      markers [integrin alpha X (ITGAX) and CLEC9A] in human colorectal tumor samples. 
      Tumoral overexpression of DC-targeting chemokines had little or no effect on 
      tumor cell proliferation/survival in vitro while significantly suppressing tumor 
      growth in vivo. Fluorescence-activated cell sorting (FACS) analysis showed that 
      CCL19, CCL21, and XCL1 boosted the ratios of DCs and T cells in CD45(+) 
      leukocytes while CCL3 increased the percentage of CD45(+) leukocytes in total 
      cells in MC38 tumor. XCL1 had an additional positive effect on antigen uptake by 
      DCs in the TME and antigen transfer to tumor-draining lymph nodes. CONCLUSIONS: 
      CCL3, CCL19, CCL21, and XCL1 exhibited potent anti-tumor activities in vivo, 
      although they might differentially regulate immune cells in the TME and antigen 
      transfer to lymph nodes.
CI  - (c) The Author(s) 2022.
FAU - Yuan, Pengkun
AU  - Yuan P
AD  - School of Biomedical Engineering, Med-X Research Institute, Shanghai Jiao Tong 
      University, Shanghai 200030, China.
AD  - Clinical Stem Cell Research Center, Renji Hospital, School of Medicine, Shanghai 
      Jiao Tong University, Shanghai 200127, China.
AD  - Zhejiang University-University of Edinburgh (ZJU-UoE) Institute, Zhejiang 
      University School of Medicine, Hangzhou 310058, Zhejiang, China.
FAU - Zhou, Yunyi
AU  - Zhou Y
AD  - School of Biomedical Engineering, Med-X Research Institute, Shanghai Jiao Tong 
      University, Shanghai 200030, China.
AD  - Clinical Stem Cell Research Center, Renji Hospital, School of Medicine, Shanghai 
      Jiao Tong University, Shanghai 200127, China.
FAU - Wang, Zhixue
AU  - Wang Z
AD  - School of Biomedical Engineering, Med-X Research Institute, Shanghai Jiao Tong 
      University, Shanghai 200030, China.
AD  - Clinical Stem Cell Research Center, Renji Hospital, School of Medicine, Shanghai 
      Jiao Tong University, Shanghai 200127, China.
FAU - Gui, Liming
AU  - Gui L
AD  - School of Biomedical Engineering, Med-X Research Institute, Shanghai Jiao Tong 
      University, Shanghai 200030, China.
AD  - Clinical Stem Cell Research Center, Renji Hospital, School of Medicine, Shanghai 
      Jiao Tong University, Shanghai 200127, China.
FAU - Ma, Bin
AU  - Ma B
AUID- ORCID: 0000-0001-5744-9667
AD  - School of Biomedical Engineering, Med-X Research Institute, Shanghai Jiao Tong 
      University, Shanghai 200030, China.
AD  - Clinical Stem Cell Research Center, Renji Hospital, School of Medicine, Shanghai 
      Jiao Tong University, Shanghai 200127, China.
LA  - eng
PT  - Journal Article
DEP - 20221227
PL  - United States
TA  - Explor Target Antitumor Ther
JT  - Exploration of targeted anti-tumor therapy
JID - 101770662
PMC - PMC9834269
OTO - NOTNLM
OT  - Dendritic cells
OT  - chemokines
OT  - colorectal cancer
OT  - immunotherapy
OT  - tumor microenvironment
COIS- The authors declare that they have no conflicts of interest.
EDAT- 2023/01/20 06:00
MHDA- 2023/01/20 06:01
PMCR- 2022/12/27
CRDT- 2023/01/19 01:57
PHST- 2022/03/13 00:00 [received]
PHST- 2022/10/29 00:00 [accepted]
PHST- 2023/01/19 01:57 [entrez]
PHST- 2023/01/20 06:00 [pubmed]
PHST- 2023/01/20 06:01 [medline]
PHST- 2022/12/27 00:00 [pmc-release]
AID - etat-03-1002115 [pii]
AID - 10.37349/etat.2022.00115 [doi]
PST - ppublish
SO  - Explor Target Antitumor Ther. 2022;3(6):828-840. doi: 10.37349/etat.2022.00115. 
      Epub 2022 Dec 27.