{"title":"致突变DNA聚合酶ζ的REV7亚基作为黑色素瘤免疫检查点抑制剂治疗效果的预测性生物标志物。","authors":"Akiyoshi Hoshino, Koya Obara, Masaaki Ichinoe, Takuya Kato, Yasutaka Sakurai, Ai Ushiwata, Atsuko Umezawa, Yoshiko Numata, Masatoshi Ichihara, Yasuyuki Amoh, Yoshiki Murakumo","doi":"10.1136/jcp-2025-210213","DOIUrl":null,"url":null,"abstract":"<p><p>Immune checkpoint inhibitor (ICI) therapy serves as a standard treatment for advanced or recurrent malignant melanoma. Tumour neoantigenicity is an important factor for the effectiveness of the ICI therapy. However, the absence of reliable biomarkers to predict ICI therapy efficacy remains an unresolved challenge. REV7 is a subunit of mutagenic DNA polymerase ζ and plays a role in generating genetic alterations following DNA damage. In this study, we examined REV7 as a potential predictive biomarker for ICI therapy in melanoma. Using RNA in situ hybridisation, we assessed REV7 expression in melanomas from 42 patients who received ICI therapy. Our analysis revealed that high REV7 expression correlated significantly with improved progression-free survival, durable clinical benefit and favourable clinical outcomes according to response evaluation criteria in solid tumours. These findings suggest that REV7 may be a potential predictive biomarker for ICI therapy response in melanoma.</p>","PeriodicalId":15391,"journal":{"name":"Journal of Clinical Pathology","volume":" ","pages":""},"PeriodicalIF":2.5000,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"REV7 subunit of mutagenic DNA polymerase ζ as a predictive biomarker for the efficacy of immune checkpoint inhibitor therapy in melanoma.\",\"authors\":\"Akiyoshi Hoshino, Koya Obara, Masaaki Ichinoe, Takuya Kato, Yasutaka Sakurai, Ai Ushiwata, Atsuko Umezawa, Yoshiko Numata, Masatoshi Ichihara, Yasuyuki Amoh, Yoshiki Murakumo\",\"doi\":\"10.1136/jcp-2025-210213\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Immune checkpoint inhibitor (ICI) therapy serves as a standard treatment for advanced or recurrent malignant melanoma. Tumour neoantigenicity is an important factor for the effectiveness of the ICI therapy. However, the absence of reliable biomarkers to predict ICI therapy efficacy remains an unresolved challenge. REV7 is a subunit of mutagenic DNA polymerase ζ and plays a role in generating genetic alterations following DNA damage. In this study, we examined REV7 as a potential predictive biomarker for ICI therapy in melanoma. Using RNA in situ hybridisation, we assessed REV7 expression in melanomas from 42 patients who received ICI therapy. Our analysis revealed that high REV7 expression correlated significantly with improved progression-free survival, durable clinical benefit and favourable clinical outcomes according to response evaluation criteria in solid tumours. These findings suggest that REV7 may be a potential predictive biomarker for ICI therapy response in melanoma.</p>\",\"PeriodicalId\":15391,\"journal\":{\"name\":\"Journal of Clinical Pathology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2025-06-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Clinical Pathology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1136/jcp-2025-210213\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PATHOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Pathology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/jcp-2025-210213","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PATHOLOGY","Score":null,"Total":0}
REV7 subunit of mutagenic DNA polymerase ζ as a predictive biomarker for the efficacy of immune checkpoint inhibitor therapy in melanoma.
Immune checkpoint inhibitor (ICI) therapy serves as a standard treatment for advanced or recurrent malignant melanoma. Tumour neoantigenicity is an important factor for the effectiveness of the ICI therapy. However, the absence of reliable biomarkers to predict ICI therapy efficacy remains an unresolved challenge. REV7 is a subunit of mutagenic DNA polymerase ζ and plays a role in generating genetic alterations following DNA damage. In this study, we examined REV7 as a potential predictive biomarker for ICI therapy in melanoma. Using RNA in situ hybridisation, we assessed REV7 expression in melanomas from 42 patients who received ICI therapy. Our analysis revealed that high REV7 expression correlated significantly with improved progression-free survival, durable clinical benefit and favourable clinical outcomes according to response evaluation criteria in solid tumours. These findings suggest that REV7 may be a potential predictive biomarker for ICI therapy response in melanoma.
期刊介绍:
Journal of Clinical Pathology is a leading international journal covering all aspects of pathology. Diagnostic and research areas covered include histopathology, virology, haematology, microbiology, cytopathology, chemical pathology, molecular pathology, forensic pathology, dermatopathology, neuropathology and immunopathology. Each issue contains Reviews, Original articles, Short reports, Correspondence and more.