Inhibition of the DNA damage response to activate immune responses toward tumors

FEBS Journal ◽  
2021 ◽  
Author(s):  
Sheetal Sharma ◽  
Mrinal Srivastava
Keyword(s):  
Dna Damage ◽  
Immune Responses ◽  
Dna Damage Response ◽  
Damage Response

scholarly journals Function and Molecular Mechanism of the DNA Damage Response in Immunity and Cancer Immunotherapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Zu Ye ◽  
Yin Shi ◽  
Susan P. Lees-Miller ◽  
John A. Tainer
Keyword(s):  
Dna Damage ◽  
Immune Responses ◽  
Cancer Immunotherapy ◽  
Dna Damage Response ◽  
Immune Checkpoint ◽  
B Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Immune Checkpoint Blockade ◽  
Dna Damage And Repair ◽  
Damage Response

The DNA damage response (DDR) is an organized network of multiple interwoven components evolved to repair damaged DNA and maintain genome fidelity. Conceptually the DDR includes damage sensors, transducer kinases, and effectors to maintain genomic stability and accurate transmission of genetic information. We have recently gained a substantially improved molecular and mechanistic understanding of how DDR components are interconnected to inflammatory and immune responses to stress. DDR shapes both innate and adaptive immune pathways: (i) in the context of innate immunity, DDR components mainly enhance cytosolic DNA sensing and its downstream STimulator of INterferon Genes (STING)-dependent signaling; (ii) in the context of adaptive immunity, the DDR is needed for the assembly and diversification of antigen receptor genes that is requisite for T and B lymphocyte development. Imbalances between DNA damage and repair impair tissue homeostasis and lead to replication and transcription stress, mutation accumulation, and even cell death. These impacts from DDR defects can then drive tumorigenesis, secretion of inflammatory cytokines, and aberrant immune responses. Yet, DDR deficiency or inhibition can also directly enhance innate immune responses. Furthermore, DDR defects plus the higher mutation load in tumor cells synergistically produce primarily tumor-specific neoantigens, which are powerfully targeted in cancer immunotherapy by employing immune checkpoint inhibitors to amplify immune responses. Thus, elucidating DDR-immune response interplay may provide critical connections for harnessing immunomodulatory effects plus targeted inhibition to improve efficacy of radiation and chemotherapies, of immune checkpoint blockade, and of combined therapeutic strategies.

scholarly journals PARP mediated DNA damage response, genomic stability and immune responses

2021 ◽  
Author(s):  
Chunyan Zong ◽  
Tianyu Zhu ◽  
Jie He ◽  
Rui Huang ◽  
Renbing Jia ◽  
...  
Keyword(s):  
Dna Damage ◽  
Immune Responses ◽  
Dna Damage Response ◽  
Genomic Stability ◽  
Damage Response

2118-P: Regulation of Ataxia-Telangiectasia and Rad3-Related (ATR)–Dependent DNA Damage Response by Nitric Oxide in ß-Cells

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 2118-P
Author(s):  
CHAY TENG YEO ◽  
BRYNDON OLESON ◽  
JOHN A. CORBETT ◽  
JAMIE K. SCHNUCK
Keyword(s):  
Nitric Oxide ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Ataxia Telangiectasia ◽  
Damage Response

DNA damage response and neuroprotection

10.2741/2862 ◽  
2008 ◽  
Vol 13 (13) ◽  
pp. 2504 ◽  
Author(s):  
Inna, I. Kruman
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Damage Response
Sign in / Sign up

Export Citation Format

Share Document