[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-337043-105":59,"doc-detail-337043-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","morphine-treatment-restricts-response-to-immunotherapy-in-oral-squamous-cell-carcinoma","Morphine treatment restricts response to immunotherapy in oral squamous cell carcinoma","","Immune checkpoint inhibitors (ICIs) are standard for recurrent and metastatic cancer, yet their efficacy can be compromised by opioid use. This study tests the hypothesis that exogenous opioids suppress antitumor immunity through T cell-mediated mu opioid receptor 1 (OPRM1) signaling. In silico analyses assessed OPRM1 in tumor-infiltrating immune cells, and a syngeneic mouse model evaluated morphine and OPRM1 antagonism with anti-PD-1 therapy. Morphine reduced T-cell infiltration and anti-PD-1 efficacy, while peripherally acting OPRM1 antagonists blocked immunosuppression and restored antitumor response.",{"@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/morphine-treatment-restricts-response-to-immunotherapy-in-oral-squamous-cell-carcinoma/337043/",{"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/morphine-treatment-restricts-response-to-immunotherapy-in-oral-squamous-cell-carcinoma/337043.png","ImageObject",300,407,{"name":92,"@type":93},"Seraphina","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",17,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What problem does the study address in cancer immunotherapy?","Question",{"text":113,"@type":114},"The study addresses concerns that opioid treatment for cancer-related pain may interfere with the efficacy of immune checkpoint inhibitors (ICIs), particularly anti-PD-1 therapy.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How does morphine affect antitumor immunity in the reported experiments?",{"text":118,"@type":114},"Exogenous morphine treatment reduced CD4+ and CD8+ T-cell infiltration in tumor-bearing mice and subsequently decreased the efficacy of anti-PD-1 treatment.",{"name":120,"@type":111,"acceptedAnswer":121},"What role does OPRM1 antagonism play in the study?",{"text":122,"@type":114},"Peripherally acting mu opioid receptor (OPRM1) antagonism, given as an adjunct, blocked morphine-induced immunosuppression and recovered the antitumor efficacy of anti-PD-1 therapy.","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},337043,1790368991,{"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},962075114101,"https://ap-avatar.wpscdn.com/avatar/e000253a75eb197efd?x-image-process=image/resize,m_fixed,w_180,h_180&k=1780044092746381165","Open access Original research  \n Morphine treatment restricts response  \nto immunotherapy in oral squamous cell carcinoma  \nLisa A McIlvried,1 Andre A Martel Matos,1 Mona M Yuan,1 Megan A Atherton,1 Fendi Obuekwe,2 Marci L Nilsen,2,3 Amin Reza Nikpoor,4 Sebastien Talbot,4,5 Tullia C Bruno,6,7 David N Taggart,8 Lorin K Johnson,8 Robert L Ferris  ,6,7 Dan P Zandberg,7 Nicole N Scheff  1,7  \nTo cite: McIlvried LA, Martel Matos AA, Yuan MM, et al. Morphine treatment restricts response to immunotherapy in oral squamous cell carcinoma. Journal for ImmunoTherapy of Cancer 2024;12:e009962 . doi:10.1136/jitc-2024-009962  \n► Additional supplemental material is published online only. To view, please visit the journal online ([https://doi.org/10.1136/](https://doi.org/10.1136/)[ ](https://doi.org/10.1136/)[jitc-2024-009962](jitc-2024-009962)) .  \nAccepted 23 October 2024  \n© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.  \nFor numbered affiliations see end of article.  \nCorrespondence to  \nDr Nicole N Scheff; [nns18@pitt.edu](nns18@pitt.edu)  \nABSTRACT  \nBackground Immune checkpoint inhibitors (ICIs) are becoming the standard of care for recurrent and metastatic cancer. Opioids, the primary treatment for cancer-related pain, are immunosuppressive raising concerns about their potential to interfere with the efficacy of ICIs. We hypothesize that exogenous opioids given for analgesia suppress antitumor immunity via T cellmediated mu opioid receptor 1 (OPRM1) signaling. Methods In silico bioinformatics were used to assess OPRM1 receptor expression on tumor-infiltrating immune cells in patients with head and neck squamous cell carcinoma (HNSCC) and across different cancer types. A syngeneic orthotopic mouse model of oral squamous cell carcinoma was used to study the impact of morphine and OPRM1 antagonism on tumor-infiltrating immune cells, tumor growth and antitumor efficacy of anti-Programmed cell death protein 1 (PD-1) monoclonal antibody treatment. Results In patients with HNSCC, OPRM1 expression was most abundant in CD8+ T cells, particularly in patients who had not been prescribed opioids prior to resection and exhibited increased expression of exhaustion markers. Exogenous morphine treatment in tumor-bearing mice reduced CD4+ and CD8+ T-cell infiltration and subsequently anti-PD1 ICI efficacy. Peripherally acting mu opioid receptor antagonism, when administered in the adjunctive setting, was able to block morphine-induced immunosuppression and recover the antitumor efficacy of anti-PD1 .  \nConclusions These findings suggest that morphine acts via a peripheral OPRM1-mediated mechanism to suppress CD8+ T cells, thereby fostering a pro-tumorimpaired immune response. Importantly, peripherallyrestricted OPRM1 antagonism can effectively block this morphine-induced immunosuppression while still allowing for centrally-mediated analgesia, indicating a potential therapeutic strategy for mitigating the adverse effects of opioid pain relief in cancer treatment.  \nINTRODUCTION  \nImmune checkpoint inhibitors (ICIs) targeting the programmed cell death protein 1 (PD-1): programmed death-ligand 1 (PDL1) pathway have become the standard of care treatment for numerous solid tumors  \n\n| WHAT IS ALREADY KNOWN ON THIS TOPIC |\n| --- |\n| ⇒ Immune checkpoint inhibitors are becoming the standard of care for recurrent and metastatic cancer, but response rates remain\u003C20% in head and neck squamous cell carcinoma (HNSCC) .\u003Cbr>⇒ Cancer-related pain is a common issue at any stage of disease and opioid therapy is the primary and most dependable strategy for pain management.\u003Cbr>⇒ Opioids are immunosuppressive, directly inhibiting T cells via opioid receptors.\u003Cbr>WHAT THIS STUDY ADDS |\n| ⇒ Characterization of morphine-induced immunosuppression specific to the oral cancer tumor microenvironment.\u003Cbr>⇒ The detrimental effect of morphine on the therapeutic efficacy of anti-Programmed","cbCaibTGMCglnBSC","https://ap.wps.com/l/cbCaibTGMCglnBSC","pdf",8663892,14,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusions\n# Introduction\n## ICIs and PD-1/PD-L1 pathway\n## Opioids and immunosuppression concerns","[{\"question\":\"What problem does the study address in cancer immunotherapy?\",\"answer\":\"The study addresses concerns that opioid treatment for cancer-related pain may interfere with the efficacy of immune checkpoint inhibitors (ICIs), particularly anti-PD-1 therapy.\"},{\"question\":\"How does morphine affect antitumor immunity in the reported experiments?\",\"answer\":\"Exogenous morphine treatment reduced CD4+ and CD8+ T-cell infiltration in tumor-bearing mice and subsequently decreased the efficacy of anti-PD-1 treatment.\"},{\"question\":\"What role does OPRM1 antagonism play in the study?\",\"answer\":\"Peripherally acting mu opioid receptor (OPRM1) antagonism, given as an adjunct, blocked morphine-induced immunosuppression and recovered the antitumor efficacy of anti-PD-1 therapy.\"}]","Morphine treatment restricts response to immunotherapy in oral squamous cell carcinoma | PDF",1790017506,35]