Case report
polyfunctional synovial T cells and not single cytokine producing T cells positively correlate with disease activity, 19 suggesting they significantly contribute in propagating joint inflammation. Based on the evidence above and the patients molecular and cellular phenotype with CD4 +polyfunctional T-cell predominance on synovial biopsy, it was concluded that targeting the JAK/STAT pathway with tofacitinib was the best approach to achieve a swift response without the risk of reactivation of tumour cells in this patient. ICIs have caused a paradigm shift in oncology outcomes, although significant irAE may occur. Given ICI-induced inflammatory arthritis is a novel condition, there is currently a paucity of data on the under- lying immunological responses and optimal treatment. Recent studies suggest that ICI-induced arthritis can become chronic, 20 studies of the cellular infiltrate at the site of inflammation will inform much needed future treatment regimes. To our knowledge, this is the first case of a patient with ICI-induced inflammatory arthritis treated successfully with tofacitinib. We provide evidence that tofacitinib decreased poly- functional cytokine expressing T cells, which we and others have shown to be highly pathogenic. 17 18 In addition, we report a marked T-cell dominant synovial infiltrate with highly poly- functional CD4+ T cells and aberrant proinflammatory cytokine expression. The possibility of tumour recurrence led us away from targeting T cells directly; however, we have shown that inhibition of the JAK/STAT pathway reduces the frequency of pathogenic polyfunctional T cells, providing a profound clinical response for the patient. Given the role of JAK/STAT in regula- tion of PD-1 ligand and IFN- γ signalling in tumours, there is a theoretical risk of inducing tumour anti-PD-1 resistance. 21 To date we have not observed tumour recurrence, or indeed, signif- icant adverse effects from targeting the JAK/STAT pathway in this patient. Based on these data tofacitinib could be a promising option for the swift treatment and resolution of ICI-induced irAE. Twitter Douglas Veale @dougveale Contributors KM, AF (Aurelie Fabre, Dept of Pathology, UCD), JC (John Crown, Dept. of Oncology, UCD), DV were involved in the care of the patient. AF and UF performed and analysed the flow cytometry. CM (Ciara Murray, Dept of Pathology, UCD) and AF performed the immunohistochemical analysis. KM, AF, CM, AF, JC, UF and DV were involved in drafting the manuscript. The authors were solely responsible for final review and approval of the report. The corresponding author had final responsibility for the decision to submit for publication. Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. Competing interests None declared. Patient consent for publication Obtained. Provenance and peer review Not commissioned; externally peer reviewed.
ORCID iD Kieran Murray http://orcid.org/0 000-0001-6 201-8116
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Murray K, et al . BMJ Case Rep 2021; 14 :e238851. doi:10.1136/bcr-2020-238851
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