ArticleJournal for immunotherapy of cancer2021
ATM/NEMO signaling modulates the expression of PD-L1 following docetaxel chemotherapy in prostate cancer.
Article in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- PD-1/PD-L1 inhibitors plus chemotherapy versus chemotherapy alone for ARPI-pretreated and chemotherapy-naive metastatic castration-resistant prostate cancer: a pooled analysis of KEYNOTE-921 and CheckMate 7DX trials.International urology and nephrology · 2026Pooled it
- Tumor microenvironment-mediated immune evasion and resistance in prostate cancer: mechanisms, cross-talk, and therapeutic opportunities.Clinical and experimental medicine · 2025Review
- Targeting ATM enhances radiation sensitivity of colorectal cancer by potentiating radiation-induced cell death and antitumor immunity.Journal of advanced research · 2025Article
- Elucidating DNA Damage-Dependent Immune System Activation.International journal of molecular sciences · 2025Review
- NEMO is essential for directing the kinases IKKα and ATM to the sites of DNA damage.Science signaling · 2025Article
- Advances in the application of PD-1/PD-L1 immunotherapy for prostate cancer: a review.Frontiers in immunology · 2025Review
- Phytochemical synergies in BK002: advanced molecular docking insights for targeted prostate cancer therapy.Frontiers in pharmacology · 2025Review
- The DDR-immune fitness score: a biomarker for guiding parp and immunotherapy synergy in extensive-stage small cell lung cancer.Frontiers in oncology · 2025Review
- PD-1 inhibitor combined with Docetaxel exerts synergistic anti-prostate cancer effect in mice by down-regulating the expression of PI3K/AKT/NFKB-P65/PD-L1 signaling pathway.Cancer biomarkers : section A of Disease markers · 2024Article
- PMN-MDSCs modulated by CCL20 from cancer cells promoted breast cancer cell stemness through CXCL2-CXCR2 pathway.Signal transduction and targeted therapy · 2023Article
- Article
- Hepatocyte Transplantation Rebalances Cytokines for Hepatic Regeneration in Rats with Ataxia Telangiectasia Mutated Pathway-Related Acute Liver Failure.The American journal of pathology · 2023Article
- The anti-PD-1 era of cervical cancer: achievement, opportunity, and challenge.Frontiers in immunology · 2023Review
- CPT1A-Mediated Fatty Acid Oxidation Promotes Precursor Osteoclast Fusion in Rheumatoid Arthritis.Frontiers in immunology · 2022Article
- Anti-cancer immune responses to DNA damage response inhibitors: Molecular mechanisms and progress toward clinical translation.Frontiers in oncology · 2022Review
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe efficacy of docetaxel-based chemotherapy is limited by the development of drug resistance. Recent studies demonstrated the efficacy of anti-programmed death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) immunotherapies in metastatic prostate cancer. The ataxia telangiectasia mutation (ATM) protein plays a crucial role in maintaining genome stability and function of mitosis. Here, we aimed to determine whether PD-1/PD-L1 signaling contributes to the resistance to DTX and to elucidate the mechanism underlying DTX-induced PD-L1 expression.
methodsIn this retrospective study, PD-L1 expression was analyzed in 33 tumor tissue samples from prostate cancer patients. Prostate cell lines were used to perform functional assays and examine underlying mechanisms in vitro. A fully mouse prostate cancer model and a humanized chimeric mouse bearing human prostate tumors and peripheral blood mononuclear cells were used for in vivo assays.
resultsWe have shown that DTX, a chemotherapeutic drug which causing microtubule interference, could significantly induce the expression of PD-L1 in prostate cancer cells. This effect is blocked by the inhibition of ATM, suggesting that it plays an essential role in PD-L1 expression upregulated by DTX. Mechanistic studies have shown that ATM activity in cancer cells enhances the stability of the NF-κB essential modulator (NEMO), which leading to an increase in the NF-κB activity and PD-L1 expression. Using the mouse model, it was further demonstrated that a combination of ATM and NEMO inhibitors along with DTX augmented the antitumor efficacy of chemotherapy, which are comparable to that of PD-L1 antibody.
conclusionsOur findings have revealed that a previously unrecognized ATM-NEMO signaling which induced by DTX is capable of suppressing tumor immunity by activating the expression of PD-L1, suggesting that the ATM-NEMO-NF-κB axis can be exploited to restore the immune balance and overcome cancer resistance triggered by DTX.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.