Imperial College London
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ProfessorIainMcNeish

Faculty of Medicine, Department of Surgery & Cancer

Chair in Oncology
 
 
 
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Contact

 

+44 (0)20 7594 2185i.mcneish Website

 
 
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Assistant

 

Ms Sophie Lions +44 (0)20 7594 2792

 
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Location

 

G036Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Braund:2021:10.1016/j.celrep.2021.109412,
author = {Braund, M and Barras, D and Mina, M and Ghisoni, E and Morotti, M and Lantis, E and Fahr, N and Desbuisson, M and Grimm, A and Zhang, H and Chong, C and Dagher, J and Chee, S and Tsianou, T and Dorier, J and Stevenson, BJ and Iseli, C and Ronet, C and Bobisse, S and Genolet, R and Walton, J and Bassani-Sternberg, M and Kandalaft, LE and Ren, B and McNeish, I and Swisher, E and Harari, A and Delorenzi, M and Ciriello, G and Irving, M and Rusakiewicz, S and Foukas, PG and Martinon, F and Dangaj, D and Coukos, G},
doi = {10.1016/j.celrep.2021.109412},
journal = {Cell Reports},
pages = {1--31},
title = {Cell-autonomous inflammation of BRCA1-deficient ovarian cancers drives both tumor-intrinsic immunoreactivity and immune resistance through STING},
url = {http://dx.doi.org/10.1016/j.celrep.2021.109412},
volume = {36},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - We investigated mechanisms leading to inflammation and immunoreactivity in ovarian tumors  with  homologous  recombination  deficiency. BRCA1lossis found  to lead to transcriptional reprogramming in tumor cells and cell-intrinsic inflammation involving type I IFN and STING.BRCA1-mutated (BRCA1mut) tumors are thus T-cell inflamed at baseline. Genetic  deletion  or  methylation  of  DNA-sensing/IFN  genes  or CCL5chemokineare identified  as  potential  mechanism  to  attenuate  T cell  inflammation. Alternatively, in BRCA1mutcancersretaining inflammation, STING up regulates VEGF-A, mediating immune  resistance  and  tumor  progression. Tumor  intrinsic STING elimination  reduces neoangiogenesis,  increasesCD8+T  cell infiltration  and reverts therapeutic resistance to dual immune checkpoint blockade(ICB). VEGF-A blockade phenocopies genetic STING loss and synergizes with IC Band/or PARP inhibitors to control the outgrowth of Trp53-/-Brca1-/-but  notBrca1+/+ovarian  tumors in  vivo, offering rational combinatorial therapies for HRD cancers
AU  - Braund,M
AU  - Barras,D
AU  - Mina,M
AU  - Ghisoni,E
AU  - Morotti,M
AU  - Lantis,E
AU  - Fahr,N
AU  - Desbuisson,M
AU  - Grimm,A
AU  - Zhang,H
AU  - Chong,C
AU  - Dagher,J
AU  - Chee,S
AU  - Tsianou,T
AU  - Dorier,J
AU  - Stevenson,BJ
AU  - Iseli,C
AU  - Ronet,C
AU  - Bobisse,S
AU  - Genolet,R
AU  - Walton,J
AU  - Bassani-Sternberg,M
AU  - Kandalaft,LE
AU  - Ren,B
AU  - McNeish,I
AU  - Swisher,E
AU  - Harari,A
AU  - Delorenzi,M
AU  - Ciriello,G
AU  - Irving,M
AU  - Rusakiewicz,S
AU  - Foukas,PG
AU  - Martinon,F
AU  - Dangaj,D
AU  - Coukos,G
DO  - 10.1016/j.celrep.2021.109412
EP  - 31
PY  - 2021///
SN  - 2211-1247
SP  - 1
TI  - Cell-autonomous inflammation of BRCA1-deficient ovarian cancers drives both tumor-intrinsic immunoreactivity and immune resistance through STING
T2  - Cell Reports
UR  - http://dx.doi.org/10.1016/j.celrep.2021.109412
UR  - https://www.sciencedirect.com/science/article/pii/S2211124721008251?via%3Dihub
UR  - http://hdl.handle.net/10044/1/90059
VL  - 36
ER  -
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