[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-371753-105":59,"doc-detail-371753-en":131},{"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":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","ppp2r1a-mutations-portend-improved-survival-after-cancer-immunotherapy","PPP2R1A mutations portend improved survival after cancer immunotherapy","","Immune checkpoint blockade can treat many cancers, yet resistance limits durable benefit. A study investigated ovarian clear cell carcinoma and found significantly prolonged overall survival and progression-free survival in patients whose tumors carried PPP2R1A mutations. Findings were validated across additional ICB-treated cohorts. Tumor biopsy analyses showed enhanced IFNγ signaling and tertiary lymphoid structures at baseline, with increased immune infiltration and CD45RO+CD8+ T-cell expansion after treatment. Preclinical targeting of PPP2R1A improved survival with multiple immunotherapies, including CAR-T and ICB.",{"@graph":69,"@context":123},[70,84,106],{"@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":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/ppp2r1a-mutations-portend-improved-survival-after-cancer-immunotherapy/371753/",{"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/ppp2r1a-mutations-portend-improved-survival-after-cancer-immunotherapy/371753.png","ImageObject",300,407,{"name":92,"@type":93},"Dipper","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What is the main clinical finding regarding PPP2R1A mutations and ICB therapy?","Question",{"text":113,"@type":114},"Patients with tumors carrying PPP2R1A mutations had significantly prolonged overall survival and progression-free survival after immune checkpoint blockade.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How were the findings supported beyond the initial patient cohort?",{"text":118,"@type":114},"The results were validated in additional ICB-treated patient cohorts across multiple cancer types.",{"name":120,"@type":111,"acceptedAnswer":121},"What immune mechanisms were observed in PPP2R1A-mutated tumors after ICB treatment?",{"text":122,"@type":114},"Analyses showed enhanced IFNγ signaling, tertiary lymphoid structures at baseline, and increased immune infiltration with expansion of CD45RO+CD8+ T cells in the tumor neighbourhood.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},371753,1790471865,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},1374404997633,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","Article  \n\n| PPP2R1A mutations portend improved survival after cancer immunotherapy |  |  |\n| --- | --- | --- |\n| [https://doi.org/10.1038/s41586-025-09203-8](https://doi.org/10.1038/s41586-025-09203-8)\u003Cbr>Received: 13 November 2021 Accepted: 27 May 2025 Published online: 2 July 2025 Open access\u003Cbr> Check for updates | Yibo Dai1,2,17, Anne Knisely3,17, Mitsutake Yano4,17, Minghao Dang1,17, Emily M. Hinchcliff5, Sanghoon Lee3, Annalyn Welp6, Manoj Chelvanambi7, Matthew Lastrapes7,\u003Cbr>Heng Liu8, Zhe Yuan8, Chen Wang4, Hao Nie4, Stephanie Jean9, Luis J. Montaner8, Jiakai Hou10, Ami Patel3, Shrina Patel3, Bryan Fellman11, Ying Yuan11, Baohua Sun12, Renganayaki Krishna Pandurengan12, Edwin Roger Parra Cuentas12, Joseph Celestino3, Yan Liu13, Jinsong Liu13, R. Tyler Hillman3, Shannon N. Westin3, Anil K. Sood3,\u003Cbr>Pamela T. Soliman3, Aaron Shafer3, Larissa A. Meyer3, David M. Gershenson3,\u003Cbr>David Vining14, Dhakshinamoorthy Ganeshan14, Karen Lu3, Jennifer A. Wargo1,2,7, Weiyi Peng10, Rugang Zhang2,4,18✉, Linghua Wang1,2,15,16,18✉ & Amir A. Jazaeri2,3,18✉\u003Cbr>Immune checkpoint blockade (ICB) therapy is effective against many cancers, although resistance remains a major issue and new strategies are needed to improve clinical outcomes1–5. Here we studied ICB response ina cohort of patients with ovarian clear cell carcinoma—a cancer type that poses considerable clinical challengesand lacks effective therapies6–8. We observed significantly prolonged overall survival and progression-free survival inpatients with tumours with PPP2R1A mutations. Importantly, our findings were validated in additional ICB-treated patient cohorts across multiple cancer types. Translational analyses from tumour biopsies demonstrated enhanced IFNγ signalling, and the presence of tertiary lymphoid structures atthe baseline, as well as enhanced immune infiltration and expansion of CD45RO+CD8+ T cells in the tumour neighbourhood after ICB treatment in PPP2R1Amutated tumours. Parallel preclinical investigations showed that targeting PPP2R1A (by pharmacological inhibition or genetic modifications) in in vitro and in vivo models was associated with improved survival in the setting of treatment with several forms of immunotherapy, including chimeric antigen receptor (CAR)-T cell therapy and ICB. The results from these studies suggest that therapeutic targeting of PPP2R1Amay represent an effective strategy to improve patient outcomes after ICB or other forms of immunotherapy, although additional mechanistic and therapeutic insights are needed. |  |\n| Immune checkpoint inhibitors have revolutionized the management |  | Some data suggest that combination ICB targeting both PD-1/PD-L1 |\n| of many solid tumours but, disappointingly, have shown minimal |  | and CTLA-4 maybe more effective in recurrent ovarian cancer. A ran- |\n| efficacy in both advanced and recurrent ovarian cancer. Response |  | domized trial demonstrated a response rate of 31.4% in patients with |\n| rates to single agent programmed cell death protein 1 (PD-1) and pro- |  | recurrent epithelial ovarian cancer who received nivolumab (anti-PD1) |\n| grammed death-ligand 1 (PD-L1) inhibitors in recurrent ovarian cancer |  | plus ipilimumab (anti-CTLA-4), compared with 12.2% in those who |\n| are low1–3, ranging from 5% to 15%. Unfortunately, biomarkers, such as |  | received nivolumabalone4. Furthermore, patients in this trial with ovar- |\n| PD-L1 expression, tumour mutation burden, BRCA1/2 mutation status |  | ian clear cell carcinoma (OCCC; a rare histological subtype associated |\n| and homologous recombination deficiency, have not been significantly |  | with a worse prognosis compared with the more prevalent high-grade |\n| associated with response or clinical benefit in patients with ovarian |  | serous ovarian cancer, HGSOC6–8) demonstrated a fivefold greater |\n| cancer treated with ICB therapies3–5. |  | odds of response compared with those with HGSOC4. Thus, patients |\n\n1Department of Genomic Medicine, The ","cbCaivjJcNdr6WYO","https://ap.wps.com/l/cbCaivjJcNdr6WYO","pdf",24050120,32,"English","# Article overview\n## Study rationale and background\n## Clinical findings in ICB-treated patients\n## Translational immune analyses\n## Preclinical PPP2R1A targeting results","[{\"question\":\"What is the main clinical finding regarding PPP2R1A mutations and ICB therapy?\",\"answer\":\"Patients with tumors carrying PPP2R1A mutations had significantly prolonged overall survival and progression-free survival after immune checkpoint blockade.\"},{\"question\":\"How were the findings supported beyond the initial patient cohort?\",\"answer\":\"The results were validated in additional ICB-treated patient cohorts across multiple cancer types.\"},{\"question\":\"What immune mechanisms were observed in PPP2R1A-mutated tumors after ICB treatment?\",\"answer\":\"Analyses showed enhanced IFNγ signaling, tertiary lymphoid structures at baseline, and increased immune infiltration with expansion of CD45RO+CD8+ T cells in the tumor neighbourhood.\"}]","PPP2R1A mutations portend improved survival after cancer immunotherapy | PDF",1790192781,81]