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A 62-year-old patient with advanced hypopharyngeal squamous cell carcinoma achieved complete remission after ICI therapy, followed by surgical removal of a later pulmonary lesion. Immunohistochemistry showed HLA class I and β2-microglobulin positivity in the primary tumor but loss of these markers in the resistant recurrence, while ectopic HLA class II was present only in the primary lesion.",{"@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/hla-class-i-loss-and-resistance-to-immunotherapy-in-pulmonary-metastasis-of-hypopharyngeal-cancer/355609/",{"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/hla-class-i-loss-and-resistance-to-immunotherapy-in-pulmonary-metastasis-of-hypopharyngeal-cancer/355609.png","ImageObject",300,407,{"name":92,"@type":93},"วิน","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why can ICIs show patchy effects in head and neck cancer?","Question",{"text":112,"@type":113},"Some lesions remain partially refractory or new lesions emerge during ICI therapy, but the underlying biological reasons are not fully understood.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What happened to the patient after starting ICI therapy?",{"text":117,"@type":113},"The patient initially achieved complete remission, but a new pulmonary lesion appeared later and was surgically removed, after which durable remission continued with long-term ICI treatment.",{"name":119,"@type":110,"acceptedAnswer":120},"What immunohistochemical changes were found in the ICI-resistant pulmonary lesion?",{"text":121,"@type":113},"The resistant recurrence showed loss of HLA class I and β2-microglobulin expression, indicating reduced antigen presentation as a potential mechanism of immune escape.","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},355609,1790319952,{"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":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":34,"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},2336475104736,"https://ap-avatar.wpscdn.com/avatar/22000c4c5e0e5b17e70?x-image-process=image/resize,m_fixed,w_180,h_180&k=1786591360781797222","doi: 10.21873/invivo.14327  \nHLA Class I Loss and Resistance to Immunotherapy in Pulmonary Metastasis of Hypopharyngeal Cancer  \nAKIRA MURAKAMI1, KAORI YUKINO1, YOSHIHIRO KOMOHARA2, YUSHIMODA1, HARUKI SAITO1, YUKIO FUJIWARA2 andYORIHISA ORITA1  \n1 Departments of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan;  \n2 Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan  \nAbstract  \nBackground/Aim: Although immune checkpoint inhibitors (ICIs) can be remarkably effective in the treatment ofunresectable recurrent or metastatic carcinoma of the head and neck, even in cases ofa marked response, some lesions may remain partially refractory or new lesions may emerge. However, why ICIs sometimes produce such a patchy pattern of therapeutic effects remains unclear.  \nCase Report: A 62-year-old patient with advanced hypopharyngeal squamous cell carcinoma who developed pulmonary metastasis after surgery followed by postoperative chemoradiotherapy presented to our department. After initiating ICI therapy, the patient initially achieved complete remission; however, a new pulmonary lesion subsequently appeared and was surgically removed. The patient has since remained in durable remission with continued long-term ICI therapy. Immunohistochemical analysis comparing the new pulmonary lesion with the original hypopharyngeal tumor revealed that cancer cells in the primary lesion were positive for HLA class I and b2-microglobulin, whereas staining for these antigens was negative in cancer cells of the recurrent pulmonary lesion. Cancer cells in the primary lesion exhibited ectopic expression of HLA class II, but no expression was detected in cancer cells of recurrent lesions. Conclusion: In the pulmonary lesion that did not respond to ICIs, a loss ofHLA class I andb2-microglobulin expression was observed. These findings suggest that the reduced antigen-presenting capacity of cancer cells may contribute to immune escape.  \nKeywords: Immune checkpoint inhibitor, head and neck squamous cell carcinoma (HNSCC), pulmonary metastasis,β2-microglobulin, immune escape.  \n✉ Yoshihiro Komohara, Department of Cell Pathology, Graduate School of Medicine, Kumamoto University, 1-1-1 Honjo,  \nKumamoto, 860-8556, Japan. Tel: +81 963735095, Fax: +81 963735096, [e-mail: ycomo@kumamoto-u.ac.jp](e-mail: ycomo@kumamoto-u.ac.jp)  \nReceived January 7, 2026 | Revised February 8, 2026 | Accepted February 11, 2026  \nThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.  \n©2026 The Author(s) . Anticancer Research is published by the International Institute of Anticancer Research.  \nIntroduction  \nIn recent years, immune checkpoint inhibitors (ICIs) have become more commonly used to treat unresectable recurrent or metastatic carcinoma of the head and neck. Although ICIs have contributed to improvements in the overall survival (OS) of patients with recurrent and/or metastatic head and neck carcinoma (RM-HNC) (1, 2), only approximately one-third of patients with RM-HNC respond to multimodal treatment using ICIs, and the response rate to ICIs alone is even lower (3). A major reason why ICIs contribute to improved OS in RM-HNC is the existence of so-called ”super-responders”–patients who show an excellent response to ICIs and even achieve complete remission (CR). In such cases, surgeries that would have been unthinkable before the advent ofICIs are now being considered, such as resecting only the residual lesions that do not respond to ICIs or removing newly developed lesions that appear during ICI treatment (4). However, the reasons why some lesions respond to ICI therapy while others do not, even in super-responder cases, are still poorly understood. In the present case, we had the opportunity to observe the biological ev","cbCaigBCcqwpl2M0","https://ap.wps.com/l/cbCaigBCcqwpl2M0","pdf",1339352,"English","# Abstract\n## Background/Aim\n## Case Report\n## Conclusion\n# Introduction\n# Case Report","[{\"question\":\"Why can ICIs show patchy effects in head and neck cancer?\",\"answer\":\"Some lesions remain partially refractory or new lesions emerge during ICI therapy, but the underlying biological reasons are not fully understood.\"},{\"question\":\"What happened to the patient after starting ICI therapy?\",\"answer\":\"The patient initially achieved complete remission, but a new pulmonary lesion appeared later and was surgically removed, after which durable remission continued with long-term ICI treatment.\"},{\"question\":\"What immunohistochemical changes were found in the ICI-resistant pulmonary lesion?\",\"answer\":\"The resistant recurrence showed loss of HLA class I and β2-microglobulin expression, indicating reduced antigen presentation as a potential mechanism of immune escape.\"}]","HLA Class I Loss and Resistance to Immunotherapy in Pulmonary Metastasis of Hypopharyngeal Cancer | PDF",1790120142,18]