title: Unlocking the potential of CD70 as a novel immunotherapeutic target for non-small cell lung cancer.
abstract: Although normally restricted to activated T and B cells and mature dendritic cells, constitutive expression of CD70, a member of the tumor necrosis family, has been described in both hematological and solid tumors, where it increases tumor cell and regulatory T cell survival by signaling through its receptor, CD27.We have assessed the co-expression of CD70 and CD27 in non-small cell lung cancer (NSCLC) by immunohistochemistry to explore a correlation between expression of the protein and tumor histologic subtype, genetic aberrations and prognosis. Furthermore, we tested the ability of ARGX-110, a CD70-blocking antibody, to induce NK cell-mediated cytotoxicity.Our results revealed CD70 expression on the surface of both primary and metastatic NSCLC tumor cells and in the tumor microenvironment. Moreover, CD27-expressing tumor infiltrating lymphocytes were found adjacent to the tumor cells, suggesting active CD70-mediated signaling. Finally, we have shown that ARGX-110, has potent cytotoxic effects on CD70+ NSCLC cell lines.
authors.affiliation: Center for Oncological Research Antwerp, Center for Oncological Research Antwerp (CORE), Antwerp University, Wilrijk, Belgium.|Department of Pathology, Antwerp University Hospital, Edegem, Belgium.
authors.forename: Julie
authors.initials: J
authors.lastname: Jacobs
authors.affiliation: Department of Pathology, Antwerp University Hospital, Edegem, Belgium.
authors.forename: Karen
authors.initials: K
authors.lastname: Zwaenepoel
authors.affiliation: Center for Oncological Research Antwerp, Center for Oncological Research Antwerp (CORE), Antwerp University, Wilrijk, Belgium.|Department of Oncology, Antwerp University Hospital, Edegem, Belgium.|Phase 1-Early Clinical Trials Unit, Antwerp University Hospital, Edegem, Belgium.
authors.forename: Christian
authors.initials: C
authors.lastname: Rolfo
authors.affiliation: Center for Oncological Research Antwerp, Center for Oncological Research Antwerp (CORE), Antwerp University, Wilrijk, Belgium.
authors.forename: Jolien
authors.initials: J
authors.lastname: Van den Bossche
authors.affiliation: Center for Oncological Research Antwerp, Center for Oncological Research Antwerp (CORE), Antwerp University, Wilrijk, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Deben
authors.affiliation: arGEN-X BVBA, Ghent, Belgium.
authors.forename: Karen
authors.initials: K
authors.lastname: Silence
authors.affiliation: Center for Oncological Research Antwerp, Center for Oncological Research Antwerp (CORE), Antwerp University, Wilrijk, Belgium.|Department of Pathology, Antwerp University Hospital, Edegem, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Hermans
authors.affiliation: Center for Oncological Research Antwerp, Center for Oncological Research Antwerp (CORE), Antwerp University, Wilrijk, Belgium.|Laboratory of Experimental Hematology (LEH), Vaccine and Infectious Disease Institute, Antwerp University, Wilrijk, Belgium.
authors.forename: Evelien
authors.initials: E
authors.lastname: Smits
authors.affiliation: Department of Thoracic and Vascular Surgery, Antwerp University Hospital, Edegem, Belgium.
authors.forename: Paul
authors.initials: P
authors.lastname: Van Schil
authors.affiliation: Center for Oncological Research Antwerp, Center for Oncological Research Antwerp (CORE), Antwerp University, Wilrijk, Belgium.
authors.forename: Filip
authors.initials: F
authors.lastname: Lardon
authors.affiliation: Center for Oncological Research Antwerp, Center for Oncological Research Antwerp (CORE), Antwerp University, Wilrijk, Belgium.|Department of Pathology, Antwerp University Hospital, Edegem, Belgium.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Deschoolmeester
authors.affiliation: Center for Oncological Research Antwerp, Center for Oncological Research Antwerp (CORE), Antwerp University, Wilrijk, Belgium.|Department of Pathology, Antwerp University Hospital, Edegem, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Pauwels
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology*; D053282:CD27 Ligand / Q000096:biosynthesis* / Q000276:immunology; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology* / Q000473:pathology; D045744:Cell Line, Tumor; D018450:Disease Progression; D006801:Humans; D007116:Immunization, Passive / Q000379:methods; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000473:pathology; D058990:Molecular Targeted Therapy; D015398:Signal Transduction; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D053282:CD27 Ligand; C505771:CD70 protein, human; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
keywords: CD70; NSCLC; immunotherapy; targeted therapies