[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-328970-105":3,"detail-sidebar-cat-0-en-105":80,"doc-detail-328970-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":73,"head_meta":75,"extra_data":77,"updated_unix":79},105,"en","genomic-investigation-of-innate-sensing-pathways-in-the-tumor-microenvironment-research-open-access","Genomic investigation of innate sensing pathways in the tumor microenvironment - Research Open Access","","The innate immune system acts as the first responder to pathogens, cellular debris, and cancerous growths, coordinating antitumor T cell responses, yet its downstream signaling remains understudied due to pathway complexity. Using a mathematical framework and a custom ssGSEA-based approach, innate signaling and immunophenotypes were quantified across over 8,000 tumors from TCGA. Innate activation predicted patient mortality in subsets of cancers and PHF genes linked genomic stability with innate activation; PHF knockdown increased cell death and IFNB1 in a cGAS-dependent manner, associating innate activity with immunogenicity and intratumor microbes.",{"@graph":14,"@context":72},[15,34,55],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/genomic-investigation-of-innate-sensing-pathways-in-the-tumor-microenvironment-research-open-access/328970/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/genomic-investigation-of-innate-sensing-pathways-in-the-tumor-microenvironment-research-open-access/328970.png","ImageObject",300,407,{"name":42,"@type":43},"Miles","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-23","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":33},"InteractionCounter",{"@type":54},"ViewAction",{"@type":56,"mainEntity":57},"FAQPage",[58,64,68],{"name":59,"@type":60,"acceptedAnswer":61},"What data and computational approach were used to quantify innate immune pathways?","Question",{"text":62,"@type":63},"The study used a mathematical tool with a custom ssGSEA algorithm to quantify innate immune signaling cascades and immunophenotypes across more than 8,000 TCGA tumors.","Answer",{"name":65,"@type":60,"acceptedAnswer":66},"What was the relationship between innate immune activation and patient outcomes?",{"text":67,"@type":63},"Innate immune activation was predictive of patient mortality in a subset of cancers.",{"name":69,"@type":60,"acceptedAnswer":70},"How did PHF gene transcript knockdown affect cellular responses?",{"text":71,"@type":63},"Knockdown of PHF gene transcripts in vitro increased cell death and IFNB1 expression in a cGAS-dependent manner, supporting PHF genes as potential anti-tumor targets.","https://schema.org",{"og:url":32,"og:type":74,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":76,"canonical":32},"index,follow",{"doc_id":78,"site_id":7},328970,1790197288,{"code":4,"msg":81,"data":82},"success",[83,87,91,95,100,105,110,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":84,"show_sort_weight":85,"slug":86},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":88,"show_sort_weight":89,"slug":90},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":92,"show_sort_weight":93,"slug":94},"Exam",70,"exam",{"id":96,"doc_module":4,"doc_module_name":25,"category_name":97,"show_sort_weight":98,"slug":99},5,"Comic",60,"comic",{"id":101,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},6,"Technology",50,"technology",{"id":106,"doc_module":4,"doc_module_name":25,"category_name":107,"show_sort_weight":108,"slug":109},7,"Healthcare",40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":112,"slug":113},8,30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":96,"slug":129},19,"General","general",{"code":4,"msg":81,"data":131},{"doc_id":78,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":111,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":33,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145,"preview_page_count":4},13056703019404,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Quinn et al. BMC Cancer (2024) 24:1157 [https://doi.org/10.1186/s12885-024-12944-w](https://doi.org/10.1186/s12885-024-12944-w)  \nBMC Cancer  \n RESEARCH Open Access  \nGenomic investigation of innate sensing pathways in the tumor microenvironment  \nGabriella Quinn1, Gianna Maggiore2 and Bo Li1,3,4,5,6*  \nAbstract  \nThe innate immune system is the first responder to infectious agents, cellular debris, and cancerous growths. This system plays critical roles in the antitumor immune responses by boosting and priming T cell-mediated cytotoxicity but is understudied due to the complexity and redundancy of its various downstream signaling cascades. We utilized a mathematical tool to holistically quantify innate immune signaling cascades and immunophenotype over 8,000 tumors from The Cancer Genome Atlas (TCGA) . We found that innate immune activation was predictive of patient mortality in a subset of cancers. Further analysis identified PHF genes as transcripts that were associated with genomic stability and innate activation. Knockdown of PHF gene transcripts in vitro led to an increase in cell death and IFNB1 expression in a cGAS-dependent manner, validating PHF genes as potential anti-tumor targets. We also found an association between innate immune activation and both tumor immunogenicity and intratumor microbes, which highlights the versatility of this model. In conclusion, interrogating activation of innate immune signaling cascades demonstrated the importance of studying innate signaling in cancer and broadened the search for new therapeutic adjuvants.  \nKey points  \n1. The custom ssGSEA algorithm presented in this article is an effective tool for estimating innate immune activation  \n2. This algorithm highlighted a new target to increase cGAS signaling in cancer cell lines.  \n3. In colorectal cancer, innate immunity was associated with tumor immunogenicity.  \n4. Innate immunity demonstrated weak associations with intratumor microbial abundance.  \nKeywords TCGA, Innate immunity, CGAS-STING, Tumor microenvironment  \n*Correspondence: Bo Li[lib3@chop.edu](lib3@chop.edu)  \n1 Department of Immunology, UT Southwestern Medical Center, Dallas, TX, USA  \n2 Children’s Research Institute, UT Southwestern Medical Center, Dallas, TX, USA  \n3 Lyda Hill Department of Bioinformatics, UT Southwestern Medical Center, Dallas, TX, USA  \n4 Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, USA  \n5 Department of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA, USA  \n6 Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, USA  \n© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/.)[.](http://creativecommons.org/licenses/by-nc-nd/4.0/.)  \nQuinn et al. BMC Cancer (2024) 24:1157  \nIntroduction  \nWith the increasing interest and utilization of microbes as cancer therapy adjuvants [1, 2], the study of innate immune sy","cbCaim4WS8Ujw6GB","https://ap.wps.com/l/cbCaim4WS8Ujw6GB","pdf",5944325,13,"English","# Abstract\n# Key points\n# Introduction\n## Microbes as cancer therapy adjuvants\n## Innate sensing in the tumor microenvironment","[{\"question\":\"What data and computational approach were used to quantify innate immune pathways?\",\"answer\":\"The study used a mathematical tool with a custom ssGSEA algorithm to quantify innate immune signaling cascades and immunophenotypes across more than 8,000 TCGA tumors.\"},{\"question\":\"What was the relationship between innate immune activation and patient outcomes?\",\"answer\":\"Innate immune activation was predictive of patient mortality in a subset of cancers.\"},{\"question\":\"How did PHF gene transcript knockdown affect cellular responses?\",\"answer\":\"Knockdown of PHF gene transcripts in vitro increased cell death and IFNB1 expression in a cGAS-dependent manner, supporting PHF genes as potential anti-tumor targets.\"}]","Genomic investigation of innate sensing pathways in the tumor microenvironment - Research Open Access | PDF",1789981864,33]