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Ectonucleoside triphosphate diphosphohydrolase 6 (ENTPD6) shows divergent expression patterns across cancers. Increased ENTPD6 in some tumors may enable immune escape by promoting an immunosuppressive tumor microenvironment and poorer prognosis. In vivo, mutated ENTPD6 may enhance cytotoxic T-cell responses and reduce liver tumor size. Low ENTPD6 is linked to chemotherapy resistance, while ENTPD6-derived neoepitopes may improve immunotherapy efficacy. This paper analyzes dual roles and clinical utility of ENTPD6 in cancer.",{"@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":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/ectonucleoside-triphosphate-diphosphohydrolase-6-a-double-edged-sword-in-cancer-prognosis-and-therapy/406308/",{"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/ectonucleoside-triphosphate-diphosphohydrolase-6-a-double-edged-sword-in-cancer-prognosis-and-therapy/406308.png","ImageObject",300,407,{"name":92,"@type":93},"Bintang","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":14},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"How does ENTPD6 overexpression affect cancer progression and prognosis?","Question",{"text":112,"@type":113},"ENTPD6 overexpression in some tumors can promote immune-resistant tumor microenvironments, enabling evasion of antitumor immune responses and contributing to a poorer prognosis.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What potential beneficial role could a mutated ENTPD6 gene have?",{"text":117,"@type":113},"A mutated ENTPD6 gene may induce effective cytotoxic T-cell responses in vivo, which can reduce liver tumor size.",{"name":119,"@type":110,"acceptedAnswer":120},"How is ENTPD6 related to chemotherapy resistance and immunotherapy efficacy?",{"text":121,"@type":113},"Low ENTPD6 expression has been associated with chemotherapy resistance, while ENTPD6-derived neoepitopes may enhance the effectiveness of immunotherapy.","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},406308,1792183373,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":14,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":24,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144,"preview_page_count":4},962085564381,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","| W | J | C | O | World Journal of\u003Cbr>Clinical Oncology |\n| --- | --- | --- | --- | --- |\n\nSubmit a Manuscript: [https://www.f6publishing.com](https://www.f6publishing.com) World J Clin Oncol 2025 December 24; 16(12): 115789  \nDOI: 10.5306/wjco.v16.i12.115789 ISSN 2218-4333 (online)  \nLETTER TO THE EDITOR  \nEctonucleoside triphosphate diphosphohydrolase 6: A double-edged sword in cancer prognosis and therapy  \nAbdellatif Bouayad  \nSpecialty type: Oncology  \nProvenance and peer review:  \nInvited article; Externally peer reviewed.  \nPeer-review model: Single blind  \nPeer-review report’s classification Scientific Quality: Grade A  \nNovelty: Grade A  \nCreativity or Innovation: Grade A  \nScientific Significance: Grade A  \nP-Reviewer: Chen JY, Researcher, China  \nReceived: October 27, 2025  \nRevised: October 30, 2025  \nAccepted: November 20, 2025  \nPublished online: December 24, 2025  \nProcessing time: 59 Days and 6.3 Hours  \nAbdellatif Bouayad, Department of Immunology, Faculty of Medicine and Pharmacy Oujda, Mohammed First University, Oujda-Angad 60049, Oriental, Morocco  \nCorresponding author: Abdellatif Bouayad, MD, Associate Professor, Department of Immunology, Faculty of Medicine and Pharmacy Oujda, Mohammed First University, Mohammed V Avenue, Oujda-Angad 60049, Oriental, [Morocco.](Morocco. abdellatifbouayad@hotmail.fr)[ abdellatifbouayad@hotmail.fr](Morocco. abdellatifbouayad@hotmail.fr)  \nAbstract  \nMalignant diseases in both children and adults are a worldwide public health priority with a high socioeconomic burden. Ectonucleoside triphosphate diphosphohydrolase 6 (ENTPD6) molecule exhibits divergent expression patterns across different cancers. Its increased expression in some tumors may allow them to escape anti-tumor immune responses, potentially by inducing an immunosuppressive tumor microenvironment and favoring a poorer prognosis. Conversely, in vivo, a mutated ENTPD6 gene may induce effective cytotoxic T cell responses, thereby reducing liver tumor size. Additionally, low expression of ENTPD6 has been related to chemotherapy resistance, whereas specific ENTPD6-derived neoepitopes may potentially enhance the efficacy of immunotherapy. This paper analyses the dual roles and clinical utility of ENTPD6 in cancer.  \nKey Words: Ectonucleoside triphosphate diphosphohydrolase 6; Cancer; Prognosis; Therapy; Antitumor immunity  \n©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.  \nCore Tip: Ectonucleoside triphosphate diphosphohydrolase 6 (ENTPD6) has dual effects on cancer development and progression, influencing immune surveillance and immune evasion through tumor microenvironment modulation. It serves as a promising novel molecular biomarker for prognosis and for predicting cancer therapy responses. Furthermore, ENTPD6-derived neopeptide vaccines, as well as adoptive T-cell transfer using T cells engineered with T-cell receptors targeting ENTPD6, may constitute promising strategies in cancer immunotherapy.  \n WJCO  [https://www.wjgnet.com](https://www.wjgnet.com) 1 December 24, 2025  Volume 16  Issue 12   \nBouayad A. Divergent roles of ENTPD6 in cancers  \nCitation: Bouayad A. Ectonucleoside triphosphate diphosphohydrolase 6: A double-edged sword in cancer prognosis and therapy. World J Clin Oncol 2025; 16(12): 115789  \nURL: [https://www.wjgnet.com/2218-4333/full/v16/i12/115789.htm](https://www.wjgnet.com/2218-4333/full/v16/i12/115789.htm)  \nDOI: [https://dx.doi.org/10.5306/wjco.v16.i12.115789](https://dx.doi.org/10.5306/wjco.v16.i12.115789)  \nTO THE EDITOR  \nMalignant diseases in both children and adults are a worldwide public health priority with a high socioeconomic burden. Unfortunately, cancer cells often escape innate and adaptive immune responses, particularly T cell-mediated cytotoxicity. Indeed, cancer treatment may also lead to resistance and serious side effects, highly feared by physicians and patients, which need to be determined, effectively managed, and prevented. Even so","cbCaiqc1gWd6mPjm","https://ap.wps.com/l/cbCaiqc1gWd6mPjm","pdf",3373347,"English","# Letter to the Editor\n## Impact on antitumor immunity: duality of function","[{\"question\":\"How does ENTPD6 overexpression affect cancer progression and prognosis?\",\"answer\":\"ENTPD6 overexpression in some tumors can promote immune-resistant tumor microenvironments, enabling evasion of antitumor immune responses and contributing to a poorer prognosis.\"},{\"question\":\"What potential beneficial role could a mutated ENTPD6 gene have?\",\"answer\":\"A mutated ENTPD6 gene may induce effective cytotoxic T-cell responses in vivo, which can reduce liver tumor size.\"},{\"question\":\"How is ENTPD6 related to chemotherapy resistance and immunotherapy efficacy?\",\"answer\":\"Low ENTPD6 expression has been associated with chemotherapy resistance, while ENTPD6-derived neoepitopes may enhance the effectiveness of immunotherapy.\"}]","Ectonucleoside triphosphate diphosphohydrolase 6: A double-edged sword in cancer prognosis and therapy | PDF",1790564759,13]