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Early rise in brain damage markers and high ICOS expression in CD4+ and CD8+ T cells during checkpoint inhibitor-induced encephalomyelitis

Bjursten, S; Pandita, A; Zhao, Z; Fröjd, C; Ny, L; Jensen, C; Ullerstam, T; ... Levin, M; + view all (2021) Early rise in brain damage markers and high ICOS expression in CD4+ and CD8+ T cells during checkpoint inhibitor-induced encephalomyelitis. Journal for ImmunoTherapy of Cancer , 9 (7) 10.1136/jitc-2021-002732. Green open access

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Abstract

We report a case of rapid eradication of melanoma brain metastases and simultaneous near-fatal encephalomyelitis following double immune checkpoint blockade. Brain damage marker S-100B and C reactive protein increased before symptoms or signs of encephalomyelitis and peaked when the patient fell into a coma. At that point, additional brain damage markers and peripheral T cell phenotype was analyzed. The analyses were repeated four times during the patient’s recovery. Axonal damage marker neurofilament light polypeptide (NFL) and astrocytic damage marker glial fibrillar acidic protein (GFAP) were very high in blood and cerebrospinal fluid and gradually normalized after immunosuppression and intensive care. The costimulatory receptor inducible T cell costimulatory receptor (ICOS) was expressed on a high proportion of CD4+ and CD8+T cells as encephalomyelitis symptoms peaked and then gradually decreased in parallel with clinical improvement. Both single and double immune checkpoint inhibitor-treated melanoma patients with other serious immune-related adverse events (irAE) (n=9) also expressed ICOS on a significantly higher proportion of CD4+ and CD8+T cells compared with controls without irAE (n=12). In conclusion, our results suggest a potential role for ICOS on CD4+ and CD8+T cells in mediating encephalomyelitis and other serious irAE. In addition, brain damage markers in blood could facilitate early diagnosis of encephalitis.

Type: Article
Title: Early rise in brain damage markers and high ICOS expression in CD4+ and CD8+ T cells during checkpoint inhibitor-induced encephalomyelitis
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1136/jitc-2021-002732
Publisher version: http://dx.doi.org/10.1136/jitc-2021-002732
Language: English
Additional information: This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See https://creativecommons.org/licenses/by/4.0/.
Keywords: CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, autoimmunity, immunotherapy, melanoma
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10131538
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