Patients with gastrointestinal irritability after TGN1412-induced cytokine storm displayed selective expansion of gut-homing αβ and γδT cells
| Autor: | Andrew J. Stagg, Claire L. Price, Hafid O. Al-Hassi, Stella C. Knight, Nicki Panoskaltsis, Elizabeth R. Mann, Neil E. McCarthy, Nichola L. Gellatly |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
Cancer Research Gastrointestinal Diseases Receptors Antigen T-Cell alpha-beta medicine.medical_treatment Cytokine storm 0302 clinical medicine Immunology and Allergy Vδ2+ γδT cells biology IMMUNE-RESPONSES INDUCTION Receptors Antigen T-Cell gamma-delta TGN1412 Cytokine release syndrome Oncology 1107 Immunology Cytokines Original Article Immunotherapy Antibody medicine.symptom Life Sciences & Biomedicine TCR Adult EXPRESSION MAINTENANCE THERAPY Integrin Immunology Immune-related adverse events (irAEs) Antibodies Monoclonal Humanized Irritability Young Adult 03 medical and health sciences CD28 Antigens VEDOLIZUMAB medicine Humans Science & Technology business.industry TRANSPLANTATION MEMORY medicine.disease Leukocytes Mononuclear biology.protein business V delta 2(+)gamma delta T cells 030215 immunology Homing (hematopoietic) |
| Zdroj: | Cancer Immunology, Immunotherapy |
| Popis: | Following infusion of the anti-CD28 superagonist monoclonal antibody TGN1412, three of six previously healthy, young male recipients developed gastrointestinal irritability associated with increased expression of ‘gut-homing’ integrin β7 on peripheral blood αβT cells. This subset of patients with intestinal symptoms also displayed a striking and persistent expansion of putative Vδ2+ γδT cells in the circulation which declined over a 2-year period following drug infusion, concordant with subsiding gut symptoms. These data demonstrate that TGN1412-induced gastrointestinal symptoms were associated with dysregulation of the ‘gut-homing’ pool of blood αβ and γδT cells, induced directly by the antibody and/or arising from the subsequent cytokine storm. Electronic supplementary material The online version of this article (10.1007/s00262-020-02723-4) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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