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Publications

Journal Article Epublish

PubMed: 40205178 DOI: 10.1007/s00262-025-04006-2

Expression of costimulatory molecule CD70 is prognostic in small cell lung cancer.

Cancer Immunol Immunother 74(5):165

Authors: David Dora, Zsolt Megyesfalvi, Imre Vörös, Ágnes Paál, Peter Takacs, Daniela Dobos, Bence Lőrincz, Syeda Mahak Zahra Bokhari, Kenan Aloss, Gergely Pallag, Christopher Rivard, Hui Yu, Fred R Hirsch, Anikó Görbe, Zoltán V Varga, Zoltan Lohinai, Balazs Dome

Affiliations

  • Department of Anatomy, Histology, and Embryology, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
  • Department of Tumor Biology, National Koranyi Institute of Pulmonology, Budapest, Hungary.
  • Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
  • Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary.
  • Cardiometabolic and HUN-REN-SU System Pharmacology Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary.
  • Center for Pharmacology and Drug Research and Development, Semmelweis University, Budapest, Hungary.
  • Department of Pharmacology and Pharmacotherapy, HCEMM-SU Cardiometabolic Immunology Research Group, Budapest, Hungary.
  • MTA-SE Momentum Cardio-Oncology and Cardioimmunology Research Group, Budapest, Hungary.
  • Translational Medicine Institute, Semmelweis University, Tűzoltó Utca 37-47, 1094, Budapest, Hungary.
  • Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary.
  • Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, USA.
  • Center for Thoracic Oncology, Tisch Cancer Institute, Mount Sinai Health System, New York, USA.
  • Translational Medicine Institute, Semmelweis University, Tűzoltó Utca 37-47, 1094, Budapest, Hungary.
  • Department of Tumor Biology, National Koranyi Institute of Pulmonology, Budapest, Hungary.
  • Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
  • Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary.

Abstract

INTRODUCTION

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.

METHODS

In 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).

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 = 0.0078, HR: 1.795) without any correlation with CD45 + , CD8 + or CD20 + immune cell infiltrates. CD27 expression was mainly confined to the stroma, and it did not show a significant association with OS (p = 0.582). Importantly, high CD27 expression was linked to reduced CD45 + and CD8 + cell densities in the stroma. Both CD70 and CD27 were expressed on CD68 + macrophages, CD27 was expressed on CAFs, and both molecules exhibited a partial coexpression with CD3. Furthermore, patients with high CD20 + B-cell densities or the presence of tertiary lymphoid structures (TLS) had significantly improved OS (p = 0.0017, HR: 0.491), suggesting the importance of B-cell-related immune responses in SCLC prognosis.

CONCLUSION

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.

MeSH

Cells, Lung, Neoplasms, Immunotherapy, Lung Neoplasms, Small Cell Lung Carcinoma