Karen Zwaenepoel1,2, Julie Jacobs1,2, Astrid De Meulenaere3, Karen Silence4, Evelien Smits2,5, Vasiliki Siozopoulou1,2, Esther Hauben6, Christian Rolfo7,8, Sylvie Rottey3, Patrick Pauwels1,2. 1. Department of Pathology, Antwerp University Hospital, Edegem, Belgium. 2. Center for Oncological Research Antwerp, University of Antwerp, Wilrijk, Belgium. 3. Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium. 4. arGEN-X BVBA, Ghent, Belgium. 5. Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute, University of Antwerp, Wilrijk, Belgium. 6. Translational Cell and Tissue Research, Leuven University Hospital, Leuven, Belgium. 7. Department of Oncology, Antwerp University Hospital, Edegem, Belgium. 8. Phase 1-Early Clinical Trials Unit, Antwerp University Hospital, Edegem, Belgium.
Abstract
AIMS: 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. METHOD AND 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. CONCLUSION: 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.
AIMS: 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. METHOD AND 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 BRAFV600E 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. CONCLUSION: 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.
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