{
    "abstract": "Small cell lung cancer (SCLC) is a highly aggressive malignancy with poor survival outcomes. The CD70-CD27 axis has been implicated in immune regulation and tumor progression across cancers, but its role in SCLC has not yet been elucidated. This research explores the expression patterns and prognostic significance of CD70 and CD27 in early-stage SCLC.\nIn this retrospective study, we analyzed 190 surgically resected SCLC tumor samples using immunohistochemistry (IHC) for CD70 and CD27 expression and RNAscope for CD70 RNA detection. Immune infiltration was assessed using CD45, CD8, and CD20 staining. Quantification of RNAscope signals was performed using QPath software. Kaplan-Meier survival analysis and multivariate Cox regression were used to assess the prognostic impact of CD70, CD27, and immune cell infiltrates on overall survival (OS).\nCD70 was expressed in 46% of tumors, primarily within tumor nests, with lower expression in stromal areas. High CD70 expression correlated with significantly decreased OS (p\u2009=\u20090.0078, HR: 1.795) without any correlation with CD45\u2009+\u2009, CD8\u2009+\u2009or CD20\u2009+\u2009immune cell infiltrates. CD27 expression was mainly confined to the stroma, and it did not show a significant association with OS (p\u2009=\u20090.582). Importantly, high CD27 expression was linked to reduced CD45\u2009+\u2009and CD8\u2009+\u2009cell densities in the stroma. Both CD70 and CD27 were expressed on CD68\u2009+\u2009macrophages, CD27 was expressed on CAFs, and both molecules exhibited a partial coexpression with CD3. Furthermore, patients with high CD20\u2009+\u2009B-cell densities or the presence of tertiary lymphoid structures (TLS) had significantly improved OS (p\u2009=\u20090.0017, HR: 0.491), suggesting the importance of B-cell-related immune responses in SCLC prognosis.\nCD70, B-cell density and the presence of TLSs, but not CD27, emerged as a significant prognostic biomarker for OS in surgically treated SCLC, suggesting its potential as a therapeutic target.",
    "authors": [
        {
            "affiliation": "Department of Anatomy, Histology, and Embryology, Faculty of Medicine, Semmelweis University, Budapest, Hungary.",
            "firstname": "David",
            "initials": "D",
            "lastname": "Dora"
        },
        {
            "affiliation": "Department of Tumor Biology, National Koranyi Institute of Pulmonology, Budapest, Hungary.\nDivision of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.\nDepartment of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary.",
            "firstname": "Zsolt",
            "initials": "Z",
            "lastname": "Megyesfalvi"
        },
        {
            "affiliation": "Cardiometabolic and HUN-REN-SU System Pharmacology Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary.\nCenter for Pharmacology and Drug Research and Development, Semmelweis University, Budapest, Hungary.\nDepartment of Pharmacology and Pharmacotherapy, HCEMM-SU Cardiometabolic Immunology Research Group, Budapest, Hungary.\nMTA-SE Momentum Cardio-Oncology and Cardioimmunology Research Group, Budapest, Hungary.",
            "firstname": "Imre",
            "initials": "I",
            "lastname": "V\u00f6r\u00f6s"
        },
        {
            "affiliation": "Cardiometabolic and HUN-REN-SU System Pharmacology Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary.\nCenter for Pharmacology and Drug Research and Development, Semmelweis University, Budapest, Hungary.\nDepartment of Pharmacology and Pharmacotherapy, HCEMM-SU Cardiometabolic Immunology Research Group, Budapest, Hungary.\nMTA-SE Momentum Cardio-Oncology and Cardioimmunology Research Group, Budapest, Hungary.",
            "firstname": "\u00c1gnes",
            "initials": "\u00c1",
            "lastname": "Pa\u00e1l"
        },
        {
            "affiliation": "Department of Anatomy, Histology, and Embryology, Faculty of Medicine, Semmelweis University, Budapest, Hungary.",
            "firstname": "Peter",
            "initials": "P",
            "lastname": "Takacs"
        },
        {
            "affiliation": "Department of Anatomy, Histology, and Embryology, Faculty of Medicine, Semmelweis University, Budapest, Hungary.",
            "firstname": "Daniela",
            "initials": "D",
            "lastname": "Dobos"
        },
        {
            "affiliation": "Department of Anatomy, Histology, and Embryology, Faculty of Medicine, Semmelweis University, Budapest, Hungary.",
            "firstname": "Bence",
            "initials": "B",
            "lastname": "L\u0151rincz"
        },
        {
            "affiliation": "Translational Medicine Institute, Semmelweis University, T\u0171zolt\u00f3 Utca 37-47, 1094, Budapest, Hungary.",
            "firstname": "Syeda Mahak Zahra",
            "initials": "SMZ",
            "lastname": "Bokhari"
        },
        {
            "affiliation": "Translational Medicine Institute, Semmelweis University, T\u0171zolt\u00f3 Utca 37-47, 1094, Budapest, Hungary.\nDepartment of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary.",
            "firstname": "Kenan",
            "initials": "K",
            "lastname": "Aloss"
        },
        {
            "affiliation": "Department of Anatomy, Histology, and Embryology, Faculty of Medicine, Semmelweis University, Budapest, Hungary.",
            "firstname": "Gergely",
            "initials": "G",
            "lastname": "Pallag"
        },
        {
            "affiliation": "Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, USA.",
            "firstname": "Christopher",
            "initials": "C",
            "lastname": "Rivard"
        },
        {
            "affiliation": "Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, USA.",
            "firstname": "Hui",
            "initials": "H",
            "lastname": "Yu"
        },
        {
            "affiliation": "Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, USA.\nCenter for Thoracic Oncology, Tisch Cancer Institute, Mount Sinai Health System, New York, USA.",
            "firstname": "Fred R",
            "initials": "FR",
            "lastname": "Hirsch"
        },
        {
            "affiliation": "Cardiometabolic and HUN-REN-SU System Pharmacology Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary.\nCenter for Pharmacology and Drug Research and Development, Semmelweis University, Budapest, Hungary.",
            "firstname": "Anik\u00f3",
            "initials": "A",
            "lastname": "G\u00f6rbe"
        },
        {
            "affiliation": "Center for Pharmacology and Drug Research and Development, Semmelweis University, Budapest, Hungary.\nDepartment of Pharmacology and Pharmacotherapy, HCEMM-SU Cardiometabolic Immunology Research Group, Budapest, Hungary.\nMTA-SE Momentum Cardio-Oncology and Cardioimmunology Research Group, Budapest, Hungary.",
            "firstname": "Zolt\u00e1n V",
            "initials": "ZV",
            "lastname": "Varga"
        },
        {
            "affiliation": "Translational Medicine Institute, Semmelweis University, T\u0171zolt\u00f3 Utca 37-47, 1094, Budapest, Hungary. lohinai.zoltan@semmelweis.hu.",
            "firstname": "Zoltan",
            "initials": "Z",
            "lastname": "Lohinai"
        },
        {
            "affiliation": "Department of Tumor Biology, National Koranyi Institute of Pulmonology, Budapest, Hungary. balazs.dome@meduniwien.ac.at.\nDivision of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria. balazs.dome@meduniwien.ac.at.\nDepartment of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary. balazs.dome@meduniwien.ac.at.",
            "firstname": "Balazs",
            "initials": "B",
            "lastname": "Dome"
        }
    ],
    "conclusions": "CD70, B-cell density and the presence of TLSs, but not CD27, emerged as a significant prognostic biomarker for OS in surgically treated SCLC, suggesting its potential as a therapeutic target.",
    "copyrights": "\u00a9 2025. The Author(s).",
    "doi": "10.1007/s00262-025-04006-2",
    "journal": "Cancer immunology, immunotherapy : CII",
    "keywords": [
        "B-cell",
        "CD27",
        "CD70",
        "Small-cell lung cancer",
        "TLS",
        "Tumor microenvironment"
    ],
    "methods": null,
    "publication_date": "2025-04-10",
    "pubmed_id": "40205178\n18698040\n29203879\n3525985\n23716461\n32753728\n33520406\n29344893\n38470453\n22628427\n17132225\n32506804\n34200100\n35978199\n36762067\n34991665\n31154919\n28612394\n24484236\n37024479\n22280534\n21642860\n12670329\n37783508\n30280641\n31639216\n29900042\n26213107\n25951351\n22401771\n19062317\n27502728\n37423586\n38473788\n36700974\n23776334\n36787696\n15723067\n35550950\n35216676\n35279527\n25368676\n30132271\n26671750\n28789475\n33737119\n32601337\n28031480\n26223302\n34323938\n35017149\n38955418\n25613900\n8241510\n39009684\n10714685\n32700566\n30979687",
    "results": "CD70 was expressed in 46% of tumors, primarily within tumor nests, with lower expression in stromal areas. High CD70 expression correlated with significantly decreased OS (p\u2009=\u20090.0078, HR: 1.795) without any correlation with CD45\u2009+\u2009, CD8\u2009+\u2009or CD20\u2009+\u2009immune cell infiltrates. CD27 expression was mainly confined to the stroma, and it did not show a significant association with OS (p\u2009=\u20090.582). Importantly, high CD27 expression was linked to reduced CD45\u2009+\u2009and CD8\u2009+\u2009cell densities in the stroma. Both CD70 and CD27 were expressed on CD68\u2009+\u2009macrophages, CD27 was expressed on CAFs, and both molecules exhibited a partial coexpression with CD3. Furthermore, patients with high CD20\u2009+\u2009B-cell densities or the presence of tertiary lymphoid structures (TLS) had significantly improved OS (p\u2009=\u20090.0017, HR: 0.491), suggesting the importance of B-cell-related immune responses in SCLC prognosis.",
    "title": "Expression of costimulatory molecule CD70 is prognostic in small cell lung cancer.",
    "xml": "<Element 'PubmedArticle' at 0x78850385f060>"
}