General autoimmunity

Oral

pd1 and pd-l1 Expression in Graves’ Disease’s Thyroid Glands. a Clue to Better Understand the Pathogenesis and Immune Checkpoint Immunotherapy-associated Thyroid Autoimmunity

Thursday, June 15
5:45 PM - 7:00 PM

It has recently been reported that thyroid autoimmunity -including cases of Graves' disease (GD)- may arise as a consequence of the new cancer immunotherapies focused on blocking the immune checkpoints PD-1 and CTLA-4. On the other side, thyroid autoinmune tissue show a clear IFN signature, and molecules like PD-L1 are inducible by INF-gamma. The aim of the study was to investigate imnunocheckpoint molecules expresion induced by INF-gamma in thyroid samples


Cryostat sections of GD, Hashimoto thyroiditis, multinodular goiter with focal thyroiditis and lymphoid control organs were stained by single and double immunofluorescence for PD-1, PD-L1, as well as for HLA-I/II, Cytokeratin-18, TPO and lymphocyte phenotypic markers. Primary thyroid and SV-40 thyroid- derived cell line HT93 cultures were supplemented with increasing doses of IFN-gamma and stained at 48h-72h to assess HLA and PD-L1 induction.


In 11 out of 12 GD glands PD-L1 was detected clearly in thyroid follicular cells (TFCs). PD-L1 staining was confined to follicles close to lymphoid infiltrates and was much less extensive than HLA class II. In multinodular goiter glands traces of PD-L1 staining was visible in TFCs close to infiltrates. Importantly, PD1 was highly expressed by the infiltrating T cells in GD. PD-L1 expression could be readily induced by IFN-gamma in TFC cultures in a time-and dose- dependent manner, as assessed by FACS and RT-PCR.


These results suggest that silent thyroid focal thyroiditis could evolve into thyroid autoimmunity due to the release of infiltrating lymphocytes from PD1/PD1-L inhibitory interaction.

Daniel Alvarez-Sierra

PhD student
Hospital Universitari Vall d'Hebron

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    Carmen de Jesus-Gil

    Vall d'Hebron Research Institute

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      Ana Marin-Sánchez

      Immunology Division, Hospital Universitari Vall d'Hebron / Vall d'Hebron Research Institute (VHIR),

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        Isabel Caragol

        Hospital Universitari Vall d'Hebron

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          Ana Lucas

          Hospital Universitario Germans Trias i Pujol

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            Paolo Nuciforo

            Vall d'Hebron Institute of Oncology

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              Oscar Gonzalez

              Hospital Universitari Vall d'Hebron

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                Ana Casteras

                Hospital Universitari Vall d'Hebron

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                  Gabriel Obiols

                  Hospital Universitari Vall d'Hebron

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                    Ricardo Pujol-Borrell

                    Hospital Universitari Vall d'Hebron

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                      pd1 and pd-l1 Expression in Graves’ Disease’s Thyroid Glands. a Clue to Better Understand the Pathogenesis and Immune Checkpoint Immunotherapy-associated Thyroid Autoimmunity



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