title: CD70 and PD-L1 in anaplastic thyroid cancer - promising targets for immunotherapy.
abstract: OBJECTIVE
  During recent years, immune checkpoint inhibition has proved to be effective in several solid malignancies. The aim of this study was to identify novel targets for immunotherapy in anaplastic thyroid cancer by analysis of the expression of tumour antigens for which therapeutic agents are available.
  
  
  RESULTS
  By immunohistochemistry we observed tumoral expression of CD70 in 49% of cases. Expression of its receptor, CD27, was present mainly in lymphocytes surrounding and infiltrating the tumour and observed only rarely in tumour cells. CD70 expression was associated with the presence of a precursor papillary thyroid carcinoma and the presence of BRAF V600E mutations in the anaplastic thyroid cancer lesion. Furthermore, the expression of CD70 seems stable during progression of the disease. Tumoral expression of programmed cell death ligand 1 (PD-L1) was found in 28.6% of the anaplastic thyroid cancer cases. Programmed cell death 1 (PD-1), the receptor of PD-L1, was not expressed on the tumour cells. No association between CD70 expression and PD-L1 expression could be demonstrated.
  
  
  CONCLUSIONS
  These data suggest that targeted immunotherapy for CD70/CD27 and PD-L1/PD-1 might be promising in anaplastic thyroid cancer. However, as a low amount of tumour-infiltrating lymphocytes was observed in most lesions, combined therapy with agents enhancing the invasion of lymphocytes in the tumour region needs to be considered.
authors.affiliation: Department of Pathology, Antwerp University Hospital, Edegem, Belgium.|Center for Oncological Research Antwerp, University of Antwerp, Wilrijk, Belgium.
authors.forename: Karen
authors.identifier: http://orcid.org/0000-0001-9122-0639
authors.initials: K
authors.lastname: Zwaenepoel
authors.affiliation: Department of Pathology, Antwerp University Hospital, Edegem, Belgium.|Center for Oncological Research Antwerp, University of Antwerp, Wilrijk, Belgium.
authors.forename: Julie
authors.initials: J
authors.lastname: Jacobs
authors.affiliation: Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Astrid
authors.initials: A
authors.lastname: De Meulenaere
authors.affiliation: arGEN-X BVBA, Ghent, Belgium.
authors.forename: Karen
authors.initials: K
authors.lastname: Silence
authors.affiliation: Center for Oncological Research Antwerp, University of Antwerp, Wilrijk, Belgium.|Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute, University of Antwerp, Wilrijk, Belgium.
authors.forename: Evelien
authors.initials: E
authors.lastname: Smits
authors.affiliation: Department of Pathology, Antwerp University Hospital, Edegem, Belgium.|Center for Oncological Research Antwerp, University of Antwerp, Wilrijk, Belgium.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Siozopoulou
authors.affiliation: Translational Cell and Tissue Research, Leuven University Hospital, Leuven, Belgium.
authors.forename: Esther
authors.initials: E
authors.lastname: Hauben
authors.affiliation: 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: Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Rottey
authors.affiliation: Department of Pathology, Antwerp University Hospital, Edegem, Belgium.|Center for Oncological Research Antwerp, University of Antwerp, Wilrijk, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Pauwels
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000032:analysis; D060890:B7-H1 Antigen / Q000032:analysis / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D053282:CD27 Ligand / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D065646:Thyroid Carcinoma, Anaplastic; D013964:Thyroid Neoplasms
chemical_list: D000951:Antigens, Neoplasm; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; D053282:CD27 Ligand; C423236:CD274 protein, human; C505771:CD70 protein, human
keywords: BRAF; CD70; PDL1; anaplastic thyroid cancer; immunotherapy