[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-381739-105":59,"doc-detail-381739-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","chemical-carcinogens-implications-for-cancer-treatment","Chemical carcinogens: implications for cancer treatment","","Carcinogen exposure is linked to stronger cancer immunogenicity, commonly explained by neoantigen generation, yet the broader neoantigen-independent effects on anti-tumor immunity remain unclear. In this JCI issue, Huang and colleagues show that carcinogen-treated cancer cells fail to establish an immunosuppressive tumor microenvironment (TME) due to reduced M-CSF expression. Tumor-associated macrophages (TAMs) acquire anti-tumor properties instead of a conventional suppressive phenotype, extending to human lung cancers with differences between smokers and nonsmokers.",{"@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/chemical-carcinogens-implications-for-cancer-treatment/381739/",{"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/chemical-carcinogens-implications-for-cancer-treatment/381739.png","ImageObject",300,407,{"name":92,"@type":93},"supergirl","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-01","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",13,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"How do chemical carcinogens typically enhance cancer immunogenicity?","Question",{"text":113,"@type":114},"They are associated with enhanced cancer immunogenicity, often attributed to neoantigen generation from mutations.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What neoantigen-independent mechanism is highlighted in this JCI commentary?",{"text":118,"@type":114},"Carcinogen-treated cancer cells are unable to establish an immunosuppressive TME because of reduced M-CSF expression.",{"name":120,"@type":111,"acceptedAnswer":121},"What happens to tumor-associated macrophages (TAMs) after carcinogen treatment?",{"text":122,"@type":114},"TAMs reprogram into an anti-tumor phenotype rather than the conventional immunosuppressive state, influencing responses in both models and human lung cancers.","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},381739,1790701686,{"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":81,"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":39},962088121634,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","The Journal of Clinical Investigation COMMENTARY  \nChemical carcinogens: implications for cancer treatment  \nShaofeng Liu,1 Mary Saunders,1 and Tak W. Mak1,2,3,4  \n1Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. 2Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, Ontario, Canada. 3Department of Pathology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. 4Centre for Oncology and Immunology, Hong Kong Science Park, Hong Kong, China.  \nCarcinogen exposure has been associated with enhanced cancer immunogenicity that is often attributed to neoantigen generation. However, the broader, neoantigen-independent impact of carcinogenson immune responses to cancer cells remains underexplored. In  \nthis issue of the JCI, Huang et al. uncover a mechanism wherein carcinogen-treated cancer cells exhibit an inability to establish an immunosuppressive tumor microenvironment (TME) due to reduced M-CSF expression. Intriguingly, the so-called carcinogen-induced tumor-associated macrophages (TAMs) within this TME exhibited anti-tumor properties instead of the conventional immunosuppressive phenotype. This phenomenon extended to human lung cancers, as evidenced by TAM reprogramming in smokers versus nonsmokers.  \nThis study substantially advances our understanding of carcinogenmediated effects on cancer immunogenicity, potentially redirecting approaches to cancer immunotherapy.  \nCarcinogen treatment augments cancer immunogenicity beyond neoantigens  \nCarcinogens are substances with the ability to cause cancer mainly by generating mutations in cellular DNA. Carcinogens responsible for a substantial number of cancer types include high-energy radiation (e.g., UV light and X-ray irradiation), various chemicals (e.g., components of tobacco smoke, alcohol, and formaldehyde), and oncogenic viruses (e.g., HPV and HBV) (1, 2). Lung cancer is the prime example of a carcinogen-caused tumor, since 90% of these malignancies are attributable to tobacco exposure (3) . Components of tobacco smoke induce driver mutations in human bronchial epithelial  \ncells, resulting in an increased mutational burden and rampant cell-to-cell heterogeneity (3). Because carcinogen-induced malignancies contain relatively more neoantigens due to their higher mutational burden, these cancer types intrinsically exhibit enhanced immunogenicity compared with spontaneous tumors (4) . However, the DNA damage and genomic instability induced by carcinogens have additional numerous effects and can lead to innate immune activation and/or alterations to the epigenetic landscape of the genome (5–7). Delineation of the effects of these neoantigen-independent mechanisms of carcinogens on cancer immunogenicity is in its infancy.  \nIn this issue of the JCI, Huang and colleagues present an investigation of the impact of a carcinogen on cancer cell  \nRelated Article: [https://doi.org/10.1172/JCI166494](https://doi.org/10.1172/JCI166494)  \nConflict of interest: TWM holds equity in Treadwell Therapeutics Inc. and Agios Pharmaceuticals and is a consultant for AstraZeneca and Tessa Therapeutics.  \nCopyright: © 2023, Liu et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.  \nReference information: J Clin Invest. 2023;133(20):e174319 . [https://doi.org/10.1172/JCI174319](https://doi.org/10.1172/JCI174319) .  \nimmunogenicity (8). They first treated the MMTV-PyMttg (PyMt) breast cancer cell line with the carcinogen 7,12-Dimethylbenz[a]anthracene (DMBA), and selected clones (PyMt-DMBA3-4; hereafter denoted as “DMBA3-4 cells”) that had a growth rate comparable to that of control cells treated with DMSO (PyMt-DMSO3-1; hereafter denoted as “DMSO3-1 cells”.) DMBA3-4 cells showed greater immunogenicity, as they were rejected by T cells in immunocompetent mice, as expected. However, when the authors sequenced the gen","cbCaigHVipFSuCV3","https://ap.wps.com/l/cbCaigHVipFSuCV3","pdf",315600,"English","# Chemical carcinogens: implications for cancer treatment","[{\"question\":\"How do chemical carcinogens typically enhance cancer immunogenicity?\",\"answer\":\"They are associated with enhanced cancer immunogenicity, often attributed to neoantigen generation from mutations.\"},{\"question\":\"What neoantigen-independent mechanism is highlighted in this JCI commentary?\",\"answer\":\"Carcinogen-treated cancer cells are unable to establish an immunosuppressive TME because of reduced M-CSF expression.\"},{\"question\":\"What happens to tumor-associated macrophages (TAMs) after carcinogen treatment?\",\"answer\":\"TAMs reprogram into an anti-tumor phenotype rather than the conventional immunosuppressive state, influencing responses in both models and human lung cancers.\"}]","Chemical carcinogens: implications for cancer treatment | PDF",1790246833]