scholarly journals Mutations in DNA damage response pathways as a potential biomarker for immune checkpoint blockade efficacy: evidence from a seven-cancer immunotherapy cohort

Aging ◽  
2021 ◽  
Author(s):  
Wenjing Zhang ◽  
Liwen Zhang ◽  
Hao Jiang ◽  
Yuting Li ◽  
Suzhen Wang ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cancer Immunotherapy ◽  
Dna Damage Response ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Potential Biomarker ◽  
Damage Response

scholarly journals Comutations in DNA Damage Response Pathways Serve as Potential Biomarkers for Immune Checkpoint Blockade

2018 ◽  
Vol 78 (22) ◽  
pp. 6486-6496 ◽  
Author(s):  
Zhijie Wang ◽  
Jing Zhao ◽  
Guoqiang Wang ◽  
Fan Zhang ◽  
Zemin Zhang ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Damage Response ◽  
Potential Biomarkers

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 Targeting Metabolism to Control Immune Responses in Cancer and Improve Checkpoint Blockade Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5912
Author(s):  
Angèle Luby ◽  
Marie-Clotilde Alves-Guerra
Keyword(s):  
Cancer Immunotherapy ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Metabolic Pathways ◽  
Cancer Metabolism ◽  
Metabolic Stress ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
New Therapeutic Approaches ◽  
Immunosuppressive Tumor Microenvironment

Over the past decade, advances in cancer immunotherapy through PD1–PDL1 and CTLA4 immune checkpoint blockade have revolutionized the management of cancer treatment. However, these treatments are inefficient for many cancers, and unfortunately, few patients respond to these treatments. Indeed, altered metabolic pathways in the tumor play a pivotal role in tumor growth and immune response. Thus, the immunosuppressive tumor microenvironment (TME) reprograms the behavior of immune cells by altering their cellular machinery and nutrient availability to limit antitumor functions. Today, thanks to a better understanding of cancer metabolism, immunometabolism and immune checkpoint evasion, the development of new therapeutic approaches targeting the energy metabolism of cancer or immune cells greatly improve the efficacy of immunotherapy in different cancer models. Herein, we highlight the changes in metabolic pathways that regulate the differentiation of pro- and antitumor immune cells and how TME-induced metabolic stress impedes their antitumor activity. Finally, we propose some drug strategies to target these pathways in the context of cancer immunotherapy.

scholarly journals Impact of DNA Damage Response and Repair (DDR) Gene Mutations on Efficacy of PD-(L)1 Immune Checkpoint Inhibition in Non–Small Cell Lung Cancer

2020 ◽  
Vol 26 (15) ◽  
pp. 4135-4142 ◽  
Author(s):  
Biagio Ricciuti ◽  
Gonzalo Recondo ◽  
Liam F. Spurr ◽  
Yvonne Y. Li ◽  
Giuseppe Lamberti ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Immune Checkpoint ◽  
Gene Mutations ◽  
Small Cell ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Small Cell Lung ◽  
Damage Response

Cas9-edited immune checkpoint blockade PD-1 DNA polyaptamer hydrogel for cancer immunotherapy

Biomaterials ◽  
2019 ◽  
Vol 218 ◽  
pp. 119359 ◽  
Author(s):  
Jaiwoo Lee ◽  
Quoc-Viet Le ◽  
Geon Yang ◽  
Yu-Kyoung Oh
Keyword(s):  
Cancer Immunotherapy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade
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