[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-330194-105":59,"doc-detail-330194-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","aryl-hydrocarbon-receptor-suppresses-sting-mediated-type-i-ifn-expression-in-triple-negative-breast-cancer","Aryl hydrocarbon receptor suppresses STING-mediated type I IFN expression in triple-negative breast cancer","","Triple-negative breast cancer remains aggressive with limited treatment options and frequent distant metastasis. Cancer cell-intrinsic type I interferon (IFN-I) signaling can modulate therapeutic response. This study reports that, in TNBC models, the aryl hydrocarbon receptor (AhR) suppresses IFN-I expression by inhibiting STING (stimulator of interferon genes), a central mediator of interferon production. Intratumoral STING activity is required for PARP inhibitor efficacy, and PARPi activates AhR in a BRCA1 deficiency-dependent manner, forming a negative feedback loop that limits PARPi effects.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/aryl-hydrocarbon-receptor-suppresses-sting-mediated-type-i-ifn-expression-in-triple-negative-breast-cancer/330194/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/aryl-hydrocarbon-receptor-suppresses-sting-mediated-type-i-ifn-expression-in-triple-negative-breast-cancer/330194.png","ImageObject",300,407,{"name":92,"@type":93},"Anda","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-13","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the main finding about AhR in triple-negative breast cancer?","Question",{"text":112,"@type":113},"AhR suppresses type I interferon (IFN-I) expression in TNBC by inhibiting STING activity.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does PARP inhibitor treatment relate to AhR and BRCA1 deficiency?",{"text":117,"@type":113},"PARP inhibitor (PARPi) treatment activates AhR in a BRCA1 deficiency-dependent manner, suggesting a negative feedback loop affecting PARPi efficacy.",{"name":119,"@type":110,"acceptedAnswer":120},"Why does STING matter for PARP inhibitor effectiveness?",{"text":121,"@type":113},"Intratumoral STING activity is essential for mediating the efficacy of PARP inhibitors in this setting.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},330194,1789996751,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},962075006959,"https://ap-avatar.wpscdn.com/avatar/e0002397efbe92a78e?_k=1776741047341049297","[www. nature.com/scientificreports](www. nature.com/scientificreports)  \nOPEN  \nAryl hydrocarbon receptor suppresses STING‑mediated type I IFN expression in triple‑negative breast cancer  \nJeffrey C. Martin1, Tatiane da Silva Fernandes1, Kanita A. Chaudhry1,2, Masanori Oshi2,  \nScott I. Abrams3, Kazuaki Takabe2,3, Spencer R. Rosario2,4,5 & Anna Bianchi‑Smiraglia1,2*  \nTriple‑negative breast cancer (TNBC) is one of the most aggressive types of cancer. Despite decades of intense investigation, treatment options remain limited, and rapid recurrence with distant metastases remains a significant challenge. Cancer cell‑intrinsic production of cytokines such as type I interferons (IFN‑I) is a known potent modulator of response to therapy in many cancers, including TNBC, and can influence therapeutic outcome. Here, we report that, inTNBC systems, the aryl hydrocarbon receptor (AhR) suppresses IFN‑I expression via inhibition of STImulator of Interferon Genes (STING), a key mediator of interferon production. Intratumoral STING activity is essential in mediating the efficacy of PARP inhibitors (PARPi) which are used in the treatment of cancers harboring BRCA1 deficiency. We find that, inTNBC cells, PARPi treatment activatesAhR in a BRCA1 deficiency‑dependent manner, thus suggesting the presence of a negative feedback loop aimed at modulating PARPi efficacy. Importantly, our results indicate that the combined inhibition of PARP andAhR is superior in elevating IFN‑I expression as compared to PARPi‑alone. Thus, AhR inhibition may allow for enhanced IFN‑I production upon PARPi in BRCA1‑deficient breast cancers, most of which are ofTNBC origin, and may represent a therapeutically viable strategy to enhance PARPi efficacy.  \nKeywords Aryl hydrocarbon receptor, Triple-negative breast cancer, BRCA1/2 mutations, PARP inhibitors, cGAS-STING, Type I interferons  \nTriple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer that lacks the expression of targetable molecular features, mainly ER, PR and HER2 receptors1. These tumors account for roughly 15–20% of all breast cancer cases and due to the relative lack of consistent genetic or molecular features, treatment options remain limited and mainly consists of surgery and highly toxic chemotherapy2. Furthermore, TNBC displays faster rates of recurrence with distant metastasis following initial treatment of any breast cancer subtype and is associated with the worst prognosis2,3. Throughout the course of the two most recent decades, there has been a concerted effort aimed at the identification of novel therapeutic options for this disease. Importantly, the use of immunotherapy (atezolizumab, an anti-PD-L1 monoclonal antibody) in combination with chemotherapy was recently approved for use as first-line therapy in metastatic TNBC tumors that overexpress PD-L1, owing to the potential for immunomodulation as a therapeutic opportunity for this indication4. However, only a fraction of patients responds to immune checkpoint blockade and most of these patients will relapse with distal recurrent disease, highlighting the importance to improve therapeutic responses5.  \nTumors that harbor defects in homologous recombination repair (HRR), mainly homozygous BRCA1/2 mutations, have benefited from the introduction of inhibitors of the Poly-ADP Ribose Polymerase-1 (PARP1), an enzyme involved in DNA break repair6. The majority of hereditary BRCA-associated breast cancer tumors have the molecular features ofTNBC7 and typically receive a regimen of chemotherapy centered around the use of PARP1 inhibitors (PARPi)8. While the use of PARPi has significantly improved the progression-free survival of patients with advanced HRR-deficient ovarian cancer9, the long-term response rates among breast cancer  \n1Department of Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA. 2Department of Breast Surgery, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA. 3Department of Im","cbCaivCwpvhhyhKi","https://ap.wps.com/l/cbCaivCwpvhhyhKi","pdf",6051671,13,"English","# Background\n## Triple-negative breast cancer and immune response\n## Role of PARP inhibitors and STING\n# Mechanistic findings\n## AhR-mediated suppression of IFN-I\n## PARPi-driven AhR activation in BRCA1 deficiency\n# Therapeutic implications\n## Combined PARP and AhR inhibition","[{\"question\":\"What is the main finding about AhR in triple-negative breast cancer?\",\"answer\":\"AhR suppresses type I interferon (IFN-I) expression in TNBC by inhibiting STING activity.\"},{\"question\":\"How does PARP inhibitor treatment relate to AhR and BRCA1 deficiency?\",\"answer\":\"PARP inhibitor (PARPi) treatment activates AhR in a BRCA1 deficiency-dependent manner, suggesting a negative feedback loop affecting PARPi efficacy.\"},{\"question\":\"Why does STING matter for PARP inhibitor effectiveness?\",\"answer\":\"Intratumoral STING activity is essential for mediating the efficacy of PARP inhibitors in this setting.\"}]","Aryl hydrocarbon receptor suppresses STING-mediated type I IFN expression in triple-negative breast cancer | PDF",1789987617,33]