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Bridging therapy-induced phenotypes and genetic immune dysregulation to study interleukin-2-induced immunotoxicology.
Clin Immunol
September 2024
Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Member of the Fraunhofer Cluster of Excellence Immune-Mediated Diseases CIMD, Hannover, Germany. Electronic address:
Interleukin-2 (IL-2) holds promise for the treatment of cancer and autoimmune diseases, but its high-dose usage is associated with systemic immunotoxicity. Differential IL-2 receptor (IL-2R) regulation might impact function of cells upon IL-2 stimulation, possibly inducing cellular changes similar to patients with hypomorphic IL2RB mutations, presenting with multiorgan autoimmunity. Here, we show that sustained high-dose IL-2 stimulation of human lymphocytes drastically reduces IL-2Rβ surface expression especially on T cells, resulting in impaired IL-2R signaling which correlates with high IL-2Rα baseline expression.
View Article and Find Full Text PDFInterleukin-2-induced skin inflammation.
Eur J Immunol
April 2024
Department of Dermatology, University of California, San Francisco, California, USA.
Recombinant human IL-2 has been used to treat inflammatory diseases and cancer; however, side effects like skin rashes limit the use of this therapeutic. To identify key molecules and cells inducing this side effect, we characterized IL-2-induced cutaneous immune reactions and investigated the relevance of CD25 (IL-2 receptor α) in the process. We injected IL-2 intradermally into WT mice and observed increases in immune cell subsets in the skin with preferential increases in frequencies of IL-4- and IL-13-producing group 2 innate lymphoid cells and IL-17-producing dermal γδ T cells.
View Article and Find Full Text PDFAdoptive immunotherapy with interleukin-2 & induced killer cells in non-small cell lung cancer: A systematic review & meta-analysis.
Indian J Med Res
May 2016
Evidence Based Medicine Centre, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road; The First Clinical Medicine College of Lanzhou University, 1 Donggang West Road, Chengguan District, Lanzhou, Gansu, PR China.
Background & Objectives: The effectiveness of interleukin-2 (IL-2) and induced killer cells for non-small cell lung cancer (NSCLC) is controversial. This study evaluates the efficacy and safety of interleukin-2 and induced killer cells on NSCLC, so as to provide references for further clinical practice and research.
Methods: Relevant randomized controlled trials (RCTs) were searched in Cochrane library (Issue 2, 2013), Web of Science (1980-March 2013), PubMed (1966-March 2013), China Knowledge Resource Integrated database (CNKI) (1994-March 2013), China Biology Medicine database (CBM) (1978-March 2013), VIP (1989-March 2013), and Wan Fang databases (1997-March 2013).
High-dose interleukin 2 (HD-IL2) is one of the therapeutic options for patients with metastatic renal cell carcinoma. In well-selected patients with favorable clinical and pathologic features, it offers impressive response and potential long-term remission. It also has a place for treatment for metastatic malignant melanoma and in adoptive cell therapy.
View Article and Find Full Text PDFInterleukin-2-induced graft-versus-leukemia for the treatment of AML in a BRCA2 Fanconi anemia patient.
J Pediatr Hematol Oncol
March 2014
*School of Clinical Medicine, University of Cambridge, Cambridge, UK †Division of Blood and Marrow Transplantation, Levine Children's Hospital, Charlotte, NC.
Biallelic BRCA2 mutations occur in 2% of patients with Fanconi anemia and are associated with a high risk of acute leukemia at an early age and a poor prognosis. For the first time, we report the use of interleukin-2 to stimulate a graft-versus-leukemia effect and induce complete remission in a patient with BRCA2 Fanconi anemia and refractory acute myelogenous leukemia, suggesting the potential of immunotherapy in this setting. Interleukin-2 was associated with significant infusion-related toxicity.
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