PMID- 33643790
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231110
IS  - 2198-3844 (Print)
IS  - 2198-3844 (Electronic)
IS  - 2198-3844 (Linking)
VI  - 8
IP  - 4
DP  - 2021 Feb
TI  - Senescent Tumor Cells Build a Cytokine Shield in Colorectal Cancer.
PG  - 2002497
LID - 10.1002/advs.202002497 [doi]
LID - 2002497
AB  - Cellular senescence can either support or inhibit cancer progression. Here, it is 
      shown that intratumoral infiltration of CD8(+) T cells is negatively associated 
      with the proportion of senescent tumor cells in colorectal cancer (CRC). Gene 
      expression analysis reveals increased expression of C-X-C motif chemokine ligand 
      12 (CXCL12) and colony stimulating factor 1 (CSF1) in senescent tumor cells. 
      Senescent tumor cells inhibit CD8(+) T cell infiltration by secreting a high 
      concentration of CXCL12, which induces a loss of CXCR4 in T cells that result in 
      impaired directional migration. CSF1 from senescent tumor cells enhance monocyte 
      differentiation into M2 macrophages, which inhibit CD8(+) T cell activation. 
      Neutralization of CXCL12/CSF1 increases the effect of anti-PD1 antibody in 
      allograft tumors. Furthermore, inhibition of CXCL12 from senescent tumor cells 
      enhances T cell infiltration and results in reducing the number and size of 
      tumors in azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CRC. These 
      findings suggest senescent tumor cells generate a cytokine barrier protecting 
      nonsenescent tumor cells from immune attack and provide a new target for 
      overcoming the immunotherapy resistance of CRC.
CI  - (c) 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.
FAU - Choi, Yong Won
AU  - Choi YW
AD  - Department of Biochemistry and Molecular Biology Ajou University School of 
      Medicine Suwon 16499 Korea.
AD  - Department of Hematology-Oncology Ajou University School of Medicine Suwon 16499 
      Korea.
AD  - Inflamm-Aging Translational Research Center Ajou University Medical Center Suwon 
      16499 Korea.
FAU - Kim, Young Hwa
AU  - Kim YH
AD  - Department of Biochemistry and Molecular Biology Ajou University School of 
      Medicine Suwon 16499 Korea.
AD  - Department of Biomedical Sciences Ajou University Graduate School of Medicine 
      Suwon 16499 Korea.
FAU - Oh, Seung Yeop
AU  - Oh SY
AD  - Department of Surgery Ajou University School of Medicine Suwon 16499 Korea.
FAU - Suh, Kwang Wook
AU  - Suh KW
AD  - Department of Surgery Ajou University School of Medicine Suwon 16499 Korea.
FAU - Kim, Young-Sam
AU  - Kim YS
AD  - Department of Biochemistry and Molecular Biology Ajou University School of 
      Medicine Suwon 16499 Korea.
AD  - Department of Biomedical Sciences Ajou University Graduate School of Medicine 
      Suwon 16499 Korea.
FAU - Lee, Ga-Yeon
AU  - Lee GY
AD  - Department of Biochemistry and Molecular Biology Ajou University School of 
      Medicine Suwon 16499 Korea.
AD  - Department of Biomedical Sciences Ajou University Graduate School of Medicine 
      Suwon 16499 Korea.
FAU - Yoon, Jung Eun
AU  - Yoon JE
AD  - Department of Biochemistry and Molecular Biology Ajou University School of 
      Medicine Suwon 16499 Korea.
AD  - Department of Biomedical Sciences Ajou University Graduate School of Medicine 
      Suwon 16499 Korea.
FAU - Park, Soon Sang
AU  - Park SS
AD  - Department of Biochemistry and Molecular Biology Ajou University School of 
      Medicine Suwon 16499 Korea.
AD  - Department of Biomedical Sciences Ajou University Graduate School of Medicine 
      Suwon 16499 Korea.
FAU - Lee, Young-Kyoung
AU  - Lee YK
AD  - Department of Biochemistry and Molecular Biology Ajou University School of 
      Medicine Suwon 16499 Korea.
AD  - Inflamm-Aging Translational Research Center Ajou University Medical Center Suwon 
      16499 Korea.
AD  - Department of Biomedical Sciences Ajou University Graduate School of Medicine 
      Suwon 16499 Korea.
FAU - Park, Yoo Jung
AU  - Park YJ
AD  - Department of Hematology-Oncology Ajou University School of Medicine Suwon 16499 
      Korea.
FAU - Kim, Hong Seok
AU  - Kim HS
AD  - Department of Molecular Medicine Inha University School of Medicine Incheon 22212 
      Korea.
FAU - Park, So Hyun
AU  - Park SH
AD  - Department of Pathology Ajou University School of Medicine Suwon 16499 Korea.
FAU - Kim, Jang-Hee
AU  - Kim JH
AD  - Inflamm-Aging Translational Research Center Ajou University Medical Center Suwon 
      16499 Korea.
AD  - Department of Pathology Ajou University School of Medicine Suwon 16499 Korea.
FAU - Park, Tae Jun
AU  - Park TJ
AUID- ORCID: 0000-0002-8862-1834
AD  - Department of Biochemistry and Molecular Biology Ajou University School of 
      Medicine Suwon 16499 Korea.
AD  - Inflamm-Aging Translational Research Center Ajou University Medical Center Suwon 
      16499 Korea.
AD  - Department of Biomedical Sciences Ajou University Graduate School of Medicine 
      Suwon 16499 Korea.
LA  - eng
PT  - Journal Article
DEP - 20210104
PL  - Germany
TA  - Adv Sci (Weinh)
JT  - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
JID - 101664569
PMC - PMC7887594
OTO - NOTNLM
OT  - CD8+ T cells
OT  - CXCL12
OT  - cancer immunotherapy
OT  - colorectal cancers
OT  - senescent tumor cells
COIS- The authors declare no conflict of interest.
EDAT- 2021/03/02 06:00
MHDA- 2021/03/02 06:01
PMCR- 2021/01/04
CRDT- 2021/03/01 05:38
PHST- 2020/07/02 00:00 [received]
PHST- 2020/10/09 00:00 [revised]
PHST- 2021/03/01 05:38 [entrez]
PHST- 2021/03/02 06:00 [pubmed]
PHST- 2021/03/02 06:01 [medline]
PHST- 2021/01/04 00:00 [pmc-release]
AID - ADVS2253 [pii]
AID - 10.1002/advs.202002497 [doi]
PST - epublish
SO  - Adv Sci (Weinh). 2021 Jan 4;8(4):2002497. doi: 10.1002/advs.202002497. 
      eCollection 2021 Feb.