{"title":"Understanding the impact of spatial immunophenotypes on the survival of endometrial cancer patients through the ProMisE classification.","authors":"Satomi Hattori, Nobuhisa Yoshikawa, Wenting Liu, Tetsuya Matsukawa, Mei Kubokawa, Kosuke Yoshida, Masato Yoshihara, Satoshi Tamauchi, Yoshiki Ikeda, Akira Yokoi, Yusuke Shimizu, Kaoru Niimi, Hiroaki Kajiyama","doi":"10.1007/s00262-024-03919-8","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>We focused on how the immunophenotypes based on the distribution of CD8-positive tumor-infiltrating lymphocytes (TILs) relate to the endometrial cancer (EC) molecular subtypes and patients' prognosis.</p><p><strong>Patients and methods: </strong>Two cohorts of EC patients (total n = 145) were analyzed and categorized using the Molecular Risk Classifier for Endometrial cancer (ProMisE): POLEmut (POLE mutation), MMRd (mismatch repair deficiency), NSMP (no specific molecular profile), and p53abn (p53 abnormality). CD8-positive TILs, within the central tumor and the invasive margin, were examined by using immunohistochemical staining and advanced image-analysis software. It was investigated whether these immunophenotypes correlate with the molecular subtypes and patients' survival. RNA-sequencing (RNA-seq) was used to explore tumor-derived factors influencing these immunophenotypes.</p><p><strong>Results: </strong>Three distinct immunophenotypes (inflamed, excluded, and desert) based on the CD8-positive TIL patterns were identified in EC patients. Notably, the inflamed phenotype was most frequently observed in the POLEmut and MMRd subtypes, while the desert phenotype was predominant in the NSMP subtype; however, other immunophenotypes were also observed. All p53abn subtype showed the non-inflamed (excluded or desert) phenotype. The prognosis was markedly poorer in the patients with the non-inflamed phenotype than in those with the inflamed phenotype. The RNA-seq analysis showed that the expression of MYC target genes and type-1 interferon response genes was enriched in the non-inflamed phenotype in MMRd and NSMP subtypes, respectively.</p><p><strong>Conclusion: </strong>Evaluating not only the molecular classification but also the immunophenotype may lead to more personalized immunotherapy in EC and elucidating the mechanisms that underlie the formation of the three immunophenotypes could lead to the discovery of new immunotherapy targets.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 2","pages":"70"},"PeriodicalIF":4.6000,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699169/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Immunology, Immunotherapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00262-024-03919-8","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Objectives: We focused on how the immunophenotypes based on the distribution of CD8-positive tumor-infiltrating lymphocytes (TILs) relate to the endometrial cancer (EC) molecular subtypes and patients' prognosis.
Patients and methods: Two cohorts of EC patients (total n = 145) were analyzed and categorized using the Molecular Risk Classifier for Endometrial cancer (ProMisE): POLEmut (POLE mutation), MMRd (mismatch repair deficiency), NSMP (no specific molecular profile), and p53abn (p53 abnormality). CD8-positive TILs, within the central tumor and the invasive margin, were examined by using immunohistochemical staining and advanced image-analysis software. It was investigated whether these immunophenotypes correlate with the molecular subtypes and patients' survival. RNA-sequencing (RNA-seq) was used to explore tumor-derived factors influencing these immunophenotypes.
Results: Three distinct immunophenotypes (inflamed, excluded, and desert) based on the CD8-positive TIL patterns were identified in EC patients. Notably, the inflamed phenotype was most frequently observed in the POLEmut and MMRd subtypes, while the desert phenotype was predominant in the NSMP subtype; however, other immunophenotypes were also observed. All p53abn subtype showed the non-inflamed (excluded or desert) phenotype. The prognosis was markedly poorer in the patients with the non-inflamed phenotype than in those with the inflamed phenotype. The RNA-seq analysis showed that the expression of MYC target genes and type-1 interferon response genes was enriched in the non-inflamed phenotype in MMRd and NSMP subtypes, respectively.
Conclusion: Evaluating not only the molecular classification but also the immunophenotype may lead to more personalized immunotherapy in EC and elucidating the mechanisms that underlie the formation of the three immunophenotypes could lead to the discovery of new immunotherapy targets.
期刊介绍：
Cancer Immunology, Immunotherapy has the basic aim of keeping readers informed of the latest research results in the fields of oncology and immunology. As knowledge expands, the scope of the journal has broadened to include more of the progress being made in the areas of biology concerned with biological response modifiers. This helps keep readers up to date on the latest advances in our understanding of tumor-host interactions.
The journal publishes short editorials including "position papers," general reviews, original articles, and short communications, providing a forum for the most current experimental and clinical advances in tumor immunology.
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