PMID- 35145233
OWN - NLM
STAT- MEDLINE
DCOM- 20220411
LR  - 20220711
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 41
IP  - 13
DP  - 2022 Mar
TI  - Mesenchymal stromal cells equipped by IFNalpha empower T cells with potent anti-tumor 
      immunity.
PG  - 1866-1881
LID - 10.1038/s41388-022-02201-4 [doi]
AB  - Cancer treatments have been revolutionized by the emergence of immune checkpoint 
      blockade therapies. However, only a minority of patients with various tumor types 
      have benefited from such treatments. New strategies focusing on the immune 
      contexture of the tumor tissue microenvironment hold great promises. Here, we 
      created IFNalpha-overexpressing mesenchymal stromal cells (IFNalpha-MSCs). Upon direct 
      injection into tumors, we found that these cells are powerful in eliminating 
      several types of tumors. Interestingly, the intra-tumoral injection of IFNalpha-MSCs 
      could also induce specific anti-tumor effects on distant tumors. These IFNalpha-MSCs 
      promoted tumor cells to produce CXCL10, which in turn potentiates the 
      infiltration of CD8(+) T cells in the tumor site. Furthermore, IFNalpha-MSCs enhanced 
      the expression of granzyme B (GZMB) in CD8(+) T cells and invigorated their 
      cytotoxicity in a Stat3-dependent manner. Genetic ablation of Stat3 in CD8(+) T 
      cells impaired the effect of IFNalpha-MSCs on GZMB expression. Importantly, the 
      combination of IFNalpha-MSCs and PD-L1 blockade induced an even stronger anti-tumor 
      immunity. Therefore, IFNalpha-MSCs represent a novel tumor immunotherapy strategy, 
      especially when combined with PD-L1 blockade.
CI  - (c) 2022. The Author(s).
FAU - Zhang, Tao
AU  - Zhang T
AD  - CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of 
      Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy 
      of Sciences, Shanghai, 200031, China.
FAU - Wang, Yu
AU  - Wang Y
AUID- ORCID: 0000-0002-7309-7304
AD  - CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of 
      Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy 
      of Sciences, Shanghai, 200031, China.
FAU - Li, Qing
AU  - Li Q
AD  - CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of 
      Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy 
      of Sciences, Shanghai, 200031, China.
FAU - Lin, Liangyu
AU  - Lin L
AUID- ORCID: 0000-0003-4312-8955
AD  - CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of 
      Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy 
      of Sciences, Shanghai, 200031, China.
FAU - Xu, Chunliang
AU  - Xu C
AUID- ORCID: 0000-0002-4514-8477
AD  - CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of 
      Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy 
      of Sciences, Shanghai, 200031, China.
FAU - Xue, Yueqing
AU  - Xue Y
AD  - CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of 
      Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy 
      of Sciences, Shanghai, 200031, China.
FAU - Hu, Mingyuan
AU  - Hu M
AD  - CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of 
      Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy 
      of Sciences, Shanghai, 200031, China.
FAU - Shi, Yufang
AU  - Shi Y
AUID- ORCID: 0000-0001-9716-2126
AD  - CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of 
      Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy 
      of Sciences, Shanghai, 200031, China. yufangshi@sibs.ac.cn.
AD  - The Third Affiliated Hospital of Soochow University, State Key Laboratory of 
      Radiation Medicine and Protection, Institutes for Translational Medicine, Soochow 
      University Medical College, Suzhou, Jiangsu, 215123, China. yufangshi@sibs.ac.cn.
FAU - Wang, Ying
AU  - Wang Y
AUID- ORCID: 0000-0002-2571-9367
AD  - CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of 
      Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy 
      of Sciences, Shanghai, 200031, China. yingwang@sibs.ac.cn.
LA  - eng
PT  - Journal Article
DEP - 20220210
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (B7-H1 Antigen)
RN  - 0 (Interferon-alpha)
SB  - IM
MH  - B7-H1 Antigen/metabolism
MH  - CD8-Positive T-Lymphocytes
MH  - Cell Line, Tumor
MH  - Humans
MH  - Immunotherapy
MH  - Interferon-alpha
MH  - *Mesenchymal Stem Cells/metabolism
MH  - *Neoplasms/metabolism/therapy
MH  - Tumor Microenvironment
PMC - PMC8956510
COIS- The authors declare no competing interests.
EDAT- 2022/02/12 06:00
MHDA- 2022/04/12 06:00
PMCR- 2022/02/10
CRDT- 2022/02/11 05:35
PHST- 2021/08/10 00:00 [received]
PHST- 2022/01/19 00:00 [accepted]
PHST- 2021/12/22 00:00 [revised]
PHST- 2022/02/12 06:00 [pubmed]
PHST- 2022/04/12 06:00 [medline]
PHST- 2022/02/11 05:35 [entrez]
PHST- 2022/02/10 00:00 [pmc-release]
AID - 10.1038/s41388-022-02201-4 [pii]
AID - 2201 [pii]
AID - 10.1038/s41388-022-02201-4 [doi]
PST - ppublish
SO  - Oncogene. 2022 Mar;41(13):1866-1881. doi: 10.1038/s41388-022-02201-4. Epub 2022 
      Feb 10.