TY - JOUR
T1 - Neutrophils and micronuclei
T2 - An emerging link between genomic instability and cancer-driven inflammation
AU - Bui, Triet M.
AU - Sumagin, Ronen
N1 - Funding Information:
This work was supported by grants from the American Cancer Society Research Scholar Award RSG-17-235-01 , Crohn’s & Colitis Foundation Senior Research Award 624450 , National Institutes of Health DK116663 and AI153568 to RS and the Department of Defense CDMRP’s Horizon Award CA191071 to TMB.
Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2022/1/1
Y1 - 2022/1/1
N2 - Two recent studies by Bui and Butin-Israeli et al. have established the novel contribution of neutrophils to genomic instability induction and aberrant shaping of the DNA repair landscape, particularly observed in patients with inflammatory bowel diseases (IBD) and/or progressive colorectal cancer (CRC). In addition, these back-to-back studies uncovered a sharp increase in the numbers of micronuclei and lagging chromosomes in pre-cancerous and cancerous epithelium in response to prolonged PMN exposure. Given the emerging link between neutrophils and micronuclei as well as the established role of micronuclei in cGAS/STING activation, this special commentary aims to elaborate on the mechanisms by which CRC cells may adapt to neutrophil-driven genomic instability while concurrently sustain an inflamed tumor niche. We postulate that such tumor microenvironment with constant immune cell presence, inflammatory milieu, and cumulative DNA damage can drive tumor adaptation and resistance to therapeutic interventions. Finally, we discuss potential novel therapeutic approaches that can be leveraged to target this emerging neutrophil-micronuclei pathological axis, thereby preventing perpetual CRC inflammation and unwanted tumor adaptation.
AB - Two recent studies by Bui and Butin-Israeli et al. have established the novel contribution of neutrophils to genomic instability induction and aberrant shaping of the DNA repair landscape, particularly observed in patients with inflammatory bowel diseases (IBD) and/or progressive colorectal cancer (CRC). In addition, these back-to-back studies uncovered a sharp increase in the numbers of micronuclei and lagging chromosomes in pre-cancerous and cancerous epithelium in response to prolonged PMN exposure. Given the emerging link between neutrophils and micronuclei as well as the established role of micronuclei in cGAS/STING activation, this special commentary aims to elaborate on the mechanisms by which CRC cells may adapt to neutrophil-driven genomic instability while concurrently sustain an inflamed tumor niche. We postulate that such tumor microenvironment with constant immune cell presence, inflammatory milieu, and cumulative DNA damage can drive tumor adaptation and resistance to therapeutic interventions. Finally, we discuss potential novel therapeutic approaches that can be leveraged to target this emerging neutrophil-micronuclei pathological axis, thereby preventing perpetual CRC inflammation and unwanted tumor adaptation.
KW - Chromatin
KW - DNA damage
KW - Inflammation
KW - Innate immunity
KW - Tumor associated neutrophils
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U2 - 10.1016/j.mrfmmm.2022.111778
DO - 10.1016/j.mrfmmm.2022.111778
M3 - Article
C2 - 35334355
AN - SCOPUS:85126856609
VL - 824
JO - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
JF - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
SN - 0027-5107
M1 - 111778
ER -
