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Genomic instability, inflammatory signaling and response to cancer immunotherapy
- Source :
- Biochimica et Biophysica Acta (BBA) - Reviews on Cancer. 1877:188661
- Publication Year :
- 2022
- Publisher :
- Elsevier BV, 2022.
-
Abstract
- Genomic and chromosomal instability are hallmarks of cancer and shape the genomic composition of cancer cells, thereby determining their behavior and response to treatment. Various genetic and epigenetic alterations in cancer have been linked to genomic instability, including DNA repair defects, oncogene-induced replication stress, and spindle assembly checkpoint malfunction. A consequence of genomic and chromosomal instability is the leakage of DNA from the nucleus into the cytoplasm, either directly or through the formation and subsequent rupture of micronuclei. Cytoplasmic DNA subsequently activates cytoplasmic DNA sensors, triggering downstream pathways, including a type I interferon response. This inflammatory signaling has pleiotropic effects, including enhanced anti-tumor immunity and potentially results in sensitization of cancer cells to immune checkpoint inhibitors. However, cancers frequently evolve mechanisms to avoid immune clearance, including suppression of inflammatory signaling. In this review, we summarize inflammatory signaling pathways induced by various sources of genomic instability, adaptation mechanisms that suppress inflammatory signaling, and implications for cancer immunotherapy.
- Subjects :
- Genome instability
Cancer Research
DNA repair
medicine.medical_treatment
NF-KAPPA-B
Biology
Genomic Instability
03 medical and health sciences
0302 clinical medicine
Cancer immunotherapy
MISMATCH-REPAIR
Chromosomal Instability
Neoplasms
Chromosome instability
ONCOGENE-INDUCED SENESCENCE
Genetics
medicine
DNA damage repair
Humans
Epigenetics
Homologous recombination
Type I interferon
030304 developmental biology
0303 health sciences
Immune evasion
CYTOSOLIC-DNA
Cancer
DNA
medicine.disease
STING pathway
3. Good health
REPLICATION STRESS
Spindle checkpoint
DNA-DAMAGE
Oncology
STRAND BREAK REPAIR
030220 oncology & carcinogenesis
HOMOLOGOUS-RECOMBINATION
Cancer cell
Cancer research
Immune checkpoint inhibition
Immunotherapy
COPY-NUMBER ALTERATIONS
cGAS
DNA Damage
Subjects
Details
- ISSN :
- 0304419X
- Volume :
- 1877
- Database :
- OpenAIRE
- Journal :
- Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
- Accession number :
- edsair.doi.dedup.....b781b975e575dc72b4cbf83c3993346a