دورية أكاديمية
Clonally expanded CD38 hi cytotoxic CD8 T cells define the T cell infiltrate in checkpoint inhibitor-associated arthritis
| العنوان: | Clonally expanded CD38 hi cytotoxic CD8 T cells define the T cell infiltrate in checkpoint inhibitor-associated arthritis |
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| المؤلفون: | Wang, Runci, Singaraju, Anvita, Marks, Kathryne E., Shakib, Lorien, Dunlap, Garrett, Adejoorin, Ifeoluwakiisi, Greisen, Stinne R., Chen, Lin, Tirpack, Aidan K., Aude, Carlos, Fein, Miriam R., Todd, Derrick J., MacFarlane, Lindsey, Goodman, Susan M., DiCarlo, Edward F., Massarotti, Elena M., Sparks, Jeffrey A., Jonsson, A. Helena, Brenner, Michael B., Postow, Michael A., Chan, Karmela K., Bass, Anne R., Donlin, Laura T., Rao, Deepak A. |
| المصدر: | Wang , R , Singaraju , A , Marks , K E , Shakib , L , Dunlap , G , Adejoorin , I , Greisen , S R , Chen , L , Tirpack , A K , Aude , C , Fein , M R , Todd , D J , MacFarlane , L , Goodman , S M , DiCarlo , E F , Massarotti , E M , Sparks , J A , Jonsson , A H , Brenner , M B , Postow , M A , Chan , K K , Bass , .... |
| سنة النشر: | 2023 |
| المجموعة: | Aarhus University: Research |
| الوصف: | Immune checkpoint inhibitor (ICI) therapies used to treat cancer, such as anti-PD-1 antibodies, can induce autoimmune conditions in some individuals. The T cell mechanisms mediating such iatrogenic autoimmunity and their overlap with spontaneous autoimmune diseases remain unclear. Here, we compared T cells from the joints of 20 patients with an inflammatory arthritis induced by ICI therapy (ICI-arthritis) with two archetypal autoimmune arthritides, rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Single-cell transcriptomic and antigen receptor repertoire analyses highlighted clonal expansion of an activated effector CD8 T cell population in the joints and blood of patients with ICI-arthritis. These cells were identified as CD38hiCD127- CD8 T cells and were uniquely enriched in ICI-arthritis joints compared with RA and PsA and also displayed an elevated interferon signature. In vitro, type I interferon induced CD8 T cells to acquire the ICI-associated CD38hi phenotype and enhanced cytotoxic function. In a cohort of patients with advanced melanoma, ICI therapy markedly expanded circulating CD38hiCD127- T cells, which were frequently bound by the therapeutic anti-PD-1 drug. In patients with ICI-arthritis, drug-bound CD8 T cells in circulation showed marked clonal overlap with drug-bound CD8 T cells from synovial fluid. These results suggest that ICI therapy directly targets CD8 T cells in patients who develop ICI-arthritis and induces an autoimmune pathology that is distinct from prototypical spontaneous autoimmune arthritides. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://pure.au.dk/portal/en/publications/29b29817-d38c-49fb-8af4-b136c1780c05Test |
| DOI: | 10.1126/sciimmunol.add1591 |
| الإتاحة: | https://doi.org/10.1126/sciimmunol.add1591Test https://pure.au.dk/portal/en/publications/29b29817-d38c-49fb-8af4-b136c1780c05Test http://www.scopus.com/inward/record.url?scp=85166002457&partnerID=8YFLogxKTest |
| حقوق: | info:eu-repo/semantics/restrictedAccess |
| رقم الانضمام: | edsbas.9B969336 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1126/sciimmunol.add1591 |
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