PMID- 34215689
OWN - NLM
STAT- MEDLINE
DCOM- 20220111
LR  - 20220111
IS  - 2051-1426 (Electronic)
IS  - 2051-1426 (Linking)
VI  - 9
IP  - 7
DP  - 2021 Jul
TI  - Early rise in brain damage markers and high ICOS expression in CD4+ and CD8+ T 
      cells during checkpoint inhibitor-induced encephalomyelitis.
LID - 10.1136/jitc-2021-002732 [doi]
LID - e002732
AB  - 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.
CI  - (c) Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published 
      by BMJ.
FAU - Bjursten, Sara
AU  - Bjursten S
AD  - Department of Oncology, Institute of Clinical Sciences, University of Gothenburg 
      Sahlgrenska Academy, Goteborg, Sweden.
AD  - Department of Oncology, Sahlgrenska University Hospital, Goteborg, Sweden.
FAU - Pandita, Ankur
AU  - Pandita A
AD  - Department of Oncology, Institute of Clinical Sciences, University of Gothenburg 
      Sahlgrenska Academy, Goteborg, Sweden.
AD  - Department of Oncology, Sahlgrenska University Hospital, Goteborg, Sweden.
AD  - Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of 
      Medicine, University of Gothenburg Sahlgrenska Academy, Goteborg, Sweden.
FAU - Zhao, Zhiyuan
AU  - Zhao Z
AD  - Department of Oncology, Institute of Clinical Sciences, University of Gothenburg 
      Sahlgrenska Academy, Goteborg, Sweden.
AD  - Department of Oncology, Sahlgrenska University Hospital, Goteborg, Sweden.
FAU - Frojd, Charlotta
AU  - Frojd C
AD  - Department of Oncology, Sahlgrenska University Hospital, Goteborg, Sweden.
FAU - Ny, Lars
AU  - Ny L
AD  - Department of Oncology, Institute of Clinical Sciences, University of Gothenburg 
      Sahlgrenska Academy, Goteborg, Sweden.
AD  - Department of Oncology, Sahlgrenska University Hospital, Goteborg, Sweden.
FAU - Jensen, Christer
AU  - Jensen C
AD  - Department of Neuroradiology, Sahlgrenska University Hospital, Goteborg, Sweden.
FAU - Ullerstam, Tobias
AU  - Ullerstam T
AD  - Department of Anesthesiology and Intensive Care, Sahlgrenska University Hospital, 
      Goteborg, Sweden.
FAU - Jespersen, Henrik
AU  - Jespersen H
AD  - Department of Oncology, Institute of Clinical Sciences, University of Gothenburg 
      Sahlgrenska Academy, Goteborg, Sweden.
AD  - Department of Oncology, Sahlgrenska University Hospital, Goteborg, Sweden.
AD  - Department of Oncology, Akershus University Hospital, Lorenskog, Norway.
FAU - Boren, Jan
AU  - Boren J
AD  - Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of 
      Medicine, University of Gothenburg Sahlgrenska Academy, Goteborg, Sweden.
FAU - Levin, Malin
AU  - Levin M
AD  - Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of 
      Medicine, University of Gothenburg Sahlgrenska Academy, Goteborg, Sweden.
FAU - Zetterberg, Henrik
AU  - Zetterberg H
AD  - Department of Psychiatry and Neurochemistry, University of Gothenburg Institute 
      of Neuroscience and Physiology, Goteborg, Sweden.
AD  - Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Goteborg, 
      Sweden.
AD  - Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, 
      London, UK.
AD  - UK Dementia Research Institute, UCL, London, UK.
FAU - Rudin, Anna
AU  - Rudin A
AD  - Department of Rheumatology and Inflammation Research, Institute of Medicine, 
      University of Gothenburg Sahlgrenska Academy, Goteborg, Sweden.
FAU - Levin, Max
AU  - Levin M
AUID- ORCID: 0000-0001-9676-5582
AD  - Department of Oncology, Institute of Clinical Sciences, University of Gothenburg 
      Sahlgrenska Academy, Goteborg, Sweden max.levin@wlab.gu.se.
AD  - Department of Oncology, Sahlgrenska University Hospital, Goteborg, Sweden.
AD  - Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of 
      Medicine, University of Gothenburg Sahlgrenska Academy, Goteborg, Sweden.
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Immunother Cancer
JT  - Journal for immunotherapy of cancer
JID - 101620585
RN  - 0 (Biomarkers)
RN  - 0 (ICOS protein, human)
RN  - 0 (Immune Checkpoint Inhibitors)
RN  - 0 (Inducible T-Cell Co-Stimulator Protein)
SB  - IM
MH  - Aged
MH  - Biomarkers/*metabolism
MH  - Brain Damage, Chronic/*chemically induced/*genetics/pathology
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Encephalomyelitis/*chemically induced
MH  - Humans
MH  - Immune Checkpoint Inhibitors/pharmacology/*therapeutic use
MH  - Inducible T-Cell Co-Stimulator Protein/*metabolism
MH  - Male
PMC - PMC8256743
OTO - NOTNLM
OT  - CD4-Positive T-Lymphocytes
OT  - CD8-Positive T-Lymphocytes
OT  - autoimmunity
OT  - immunotherapy
OT  - melanoma
COIS- Competing interests: None declared.
EDAT- 2021/07/04 06:00
MHDA- 2022/01/12 06:00
PMCR- 2021/07/02
CRDT- 2021/07/03 05:38
PHST- 2021/06/10 00:00 [accepted]
PHST- 2021/07/03 05:38 [entrez]
PHST- 2021/07/04 06:00 [pubmed]
PHST- 2022/01/12 06:00 [medline]
PHST- 2021/07/02 00:00 [pmc-release]
AID - jitc-2021-002732 [pii]
AID - 10.1136/jitc-2021-002732 [doi]
PST - ppublish
SO  - J Immunother Cancer. 2021 Jul;9(7):e002732. doi: 10.1136/jitc-2021-002732.