التفاصيل البيبلوغرافية
| العنوان: |
Clonally expanded CD38hi cytotoxic CD8 T cells define the T cell infiltrate in checkpoint inhibitor–associated arthritis. |
| 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. |
| المصدر: |
Science Immunology; 2023, Vol. 8 Issue 85, p1-18, 18p |
| مستخلص: |
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. Editor's summary: Immune checkpoint inhibitor (ICI)–based therapies have transformed cancer treatments but have also been associated with autoimmune side effects. Wang et al. characterized T cell–mediated responses in the joints of patients with inflammatory arthritis who had received anti–PD-1–based ICI therapy (ICI-arthritis). Compared with patients with rheumatoid arthritis or psoriatic arthritis, patients with ICI-arthritis had expansion of activated effector CD38hiCD127– CD8 T cell subset in their joints that had elevated expression of IFN-associated transcripts. In vitro studies confirmed that type I IFN treatment of CD8 T cells could induce phenotypic changes consistent with CD38hiCD127– CD8 T cells. This T cell subset was also detected in a cohort of melanoma patients treated with anti–PD-1 + anti–CTLA-4. These findings provide evidence that ICI therapy can directly influence CD8 T cell responses in individuals who develop spontaneous ICI-arthritis, which is distinct from other autoimmune arthritides. —Christiana N. Fogg [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
