[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-372812-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-372812-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":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","neoadjuvant-immunotherapy-in-mismatch-repair-proficient-colon-cancers","Neoadjuvant immunotherapy in mismatch-repair-proficient colon cancers","","Neoadjuvant nivolumab plus ipilimumab followed by surgery was evaluated in the phase II NICHE study for early-stage mismatch-repair-proficient (pMMR) colon cancer. Thirty-one patients received treatment; the response rate was 26%, including six major pathological responses. Circulating tumour DNA positivity at baseline declined in responders but persisted in non-responders. Responses occurred despite low tumour mutational burden, while chromosomal genomic instability, proliferation signatures, and TCF1 were higher, and imaging mass cytometry showed more Ki-67+ cancer and Ki-67+CD8+ cells.",{"@graph":14,"@context":73},[15,34,56],{"@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/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/neoadjuvant-immunotherapy-in-mismatch-repair-proficient-colon-cancers/372812/",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/neoadjuvant-immunotherapy-in-mismatch-repair-proficient-colon-cancers/372812.png","ImageObject",300,407,{"name":42,"@type":43},"nayy☆","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-29","2026-09-23",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",9,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What treatment regimen was used in the NICHE phase II study?","Question",{"text":63,"@type":64},"Patients received neoadjuvant nivolumab plus ipilimumab, followed by surgery.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"What response rates were observed in early-stage pMMR colon cancer?",{"text":68,"@type":64},"The response rate was 26%, including six patients with major pathological response (10% or less residual viable tumour). One patient had an ongoing clinical complete response and did not undergo surgery.",{"name":70,"@type":61,"acceptedAnswer":71},"How did circulating tumour DNA relate to response?",{"text":72,"@type":64},"Circulating tumour DNA was positive in 26 of 31 patients at baseline. It cleared in 5 of 6 responders before surgery, whereas 19 of 20 non-responders remained positive.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},372812,1790247127,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},"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":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":107,"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":55,"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},962090893153,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","Article  \nNeoadjuvant immunotherapy in  \nmismatch-repair-proficient colon cancers  \n\n| [https://doi.org/10.1038/s41586-025-09679-4](https://doi.org/10.1038/s41586-025-09679-4)\u003Cbr>Received: 23 January 2025 Accepted: 24 September 2025 Published online: 20 October 2025 Open access\u003Cbr> Check for updates | Pedro B. Tan1,13, Yara L. Verschoor1,13, José G. van den Berg2, Sara Balduzzi3, Niels F. M. Kok4, Marieke E. Ijsselsteijn5, Kat Moore6, Adham Jurdi7, Antony Tin7, Paulien Kaptein8,\u003Cbr>Monique E. van Leerdam1,9, John B. A. G. Haanen8,10, Emile E. Voest8,11, Noel F. C. C. de Miranda5, Ton N. Schumacher8,11,12, Lodewyk F. A. Wessels6,11 & Myriam Chalabi1,10 ✉\u003Cbr>Immune checkpoint blockade has led to paradigm shiftsin the treatment of various tumour types1–4, yet limited efficacy has been observed inpatients with metastatic mismatch-repair-proficient (pMMR) colorectal cancer5. Here we report clinical results and in-depth analysis of patients with early-stage pMMR colon cancer from the phase II NICHE study ([ClinicalTrials.gov: NCT03026140](ClinicalTrials.gov: NCT03026140)). Atotal of 31 patients received neoadjuvant treatment of nivolumab plus ipilimumab followed by surgery. The response rate was 26% and included six patients with a major pathological response (10% or less residual viable tumour). One patient with an ongoing clinical complete response did not undergo surgery. Circulating tumour DNA was positive in 26 of 31 patients at baseline, and clearance was observed in 5 of 6 responders before surgery, whereas 19 of 20 non-responders remained circulating tumour DNA positive. Responses were observed despite a low tumour mutational burden in all tumours, whereas chromosomal genomic instability scores were significantly higher in responders than in non-responders. Furthermore, responding tumours had significantly higher baseline expression of proliferation signaturesand TCF1, and imaging mass cytometry revealed a higher percentage of Ki-67+ cancer and Ki-67+CD8+ T cells in responders than in non-responders. These results provide a comprehensive analysis of response toneoadjuvant immune checkpoint blockade in early-stage pMMR colon cancersand identify potential biomarkers for patientselection. |  |\n| --- | --- | --- |\n| Colorectal cancers (CRCs) can be divided into two biologically dis- |  | Considering the lack of efficacy ofICB in patients with metastatic |\n| tinct subtypes based on the status of the DNA MMR system: pMMR |  | pMMR CRC, and considering that pMMR tumours constitute 85% |\n| and MMR-deficient (dMMR) tumours. Although immune checkpoint |  | of non-metastatic colon cancers22, strategies aimed at the devel- |\n| blockade (ICB) has become standard of care inpatients with metastatic |  | opment of effective immunotherapy regimens for patients with |\n| dMMR tumours1,6, metastatic pMMR tumours remain largely unre- |  | non-metastatic pMMR CRC are of high interest. Preclinical data have |\n| sponsive to ICB5. This disparity has, at least in part, been attributed |  | showed that the inhibition of prostaglandin E2 synthesis, a product of |\n| to the substantially lower tumour mutational burden (TMB) seen in |  | the cyclooxygenase-2 (COX-2) pathway, suppresses tumour-promoting |\n| pMMR tumours. |  | inflammation and may enhance immunotherapy response23. |\n| In recent years, neoadjuvant ICB has shown high pathological |  | Given these data, we sought to explore the effects of neoadjuvant |\n| response rates that were associated with improved survival in vari- |  | nivolumab plus ipilimumab, with or without selective COX-2 inhibition |\n| ous solid tumour types2–4,7,8. Of note, inpatients with non-metastatic |  | using celecoxib, inpatients with early-stage pMMR colon adenocarci- |\n| dMMR CRC, neoadjuvant ICB induced remarkably high response |  | noma. Here wereport clinical outcomes as well as in-depth translational |\n| rates without disease recurrences9–13. Recent studies have also sug- |  | analyses from patients treated in thepMM","cbCaikLW71Lf0ip5","https://ap.wps.com/l/cbCaikLW71Lf0ip5","pdf",13526413,32,"English","# Article overview\n## Study design and patient treatment\n## Clinical responses and pathological outcomes\n## Biomarkers and translational analyses\n## Rationale and background on ICB in pMMR CRC","[{\"question\":\"What treatment regimen was used in the NICHE phase II study?\",\"answer\":\"Patients received neoadjuvant nivolumab plus ipilimumab, followed by surgery.\"},{\"question\":\"What response rates were observed in early-stage pMMR colon cancer?\",\"answer\":\"The response rate was 26%, including six patients with major pathological response (10% or less residual viable tumour). One patient had an ongoing clinical complete response and did not undergo surgery.\"},{\"question\":\"How did circulating tumour DNA relate to response?\",\"answer\":\"Circulating tumour DNA was positive in 26 of 31 patients at baseline. It cleared in 5 of 6 responders before surgery, whereas 19 of 20 non-responders remained positive.\"}]","Neoadjuvant immunotherapy in mismatch-repair-proficient colon cancers | PDF",1790195458,81]