Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Sconocchia, G; Lanzilli, G; Cesarini, V; Silvestris, DA; Rezvani, K; Arriga, R; Caratelli, S; Chen, K; Dou, J; Cenciarelli, C; Toietta, G; Baldari, S; Sconocchia, T; De, Paolis, F; Aureli, A; Iezzi, G; Irno, Consalvo, M; Buccisano, F; Del, Principe, MI; Maurillo, L; Venditti, A; Ottaviani, A; Spagnoli, GC.
Direct CD32 T-cell cytotoxicity: implications for breast cancer prognosis and treatment.
Life Sci Alliance. 2022; 5(12):
Doi: 10.26508/lsa.202201590
[OPEN ACCESS]
Web of Science
PubMed
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- Co-Autor*innen der Med Uni Graz
- Sconocchia Tommaso
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- Abstract:
- The FcγRII (CD32) ligands are IgFc fragments and pentraxins. The existence of additional ligands is unknown. We engineered T cells with human chimeric receptors resulting from the fusion between CD32 extracellular portion and transmembrane CD8α linked to CD28/ζ chain intracellular moiety (CD32-CR). Transduced T cells recognized three breast cancer (BC) and one colon cancer cell line among 15 tested in the absence of targeting antibodies. Sensitive BC cell conjugation with CD32-CR T cells induced CD32 polarization and down-regulation, CD107a release, mutual elimination, and proinflammatory cytokine production unaffected by human IgGs but enhanced by cetuximab. CD32-CR T cells protected immunodeficient mice from subcutaneous growth of MDA-MB-468 BC cells. RNAseq analysis identified a 42 gene fingerprint predicting BC cell sensitivity and favorable outcomes in advanced BC. ICAM1 was a major regulator of CD32-CR T cell-mediated cytotoxicity. CD32-CR T cells may help identify cell surface CD32 ligand(s) and novel prognostically relevant transcriptomic signatures and develop innovative BC treatments.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals - administration & dosage
- Breast Neoplasms - genetics, metabolism, therapy
- CD28 Antigens - metabolism
- Cetuximab - metabolism
- Female - administration & dosage
- Humans - administration & dosage
- Ligands - administration & dosage
- Mice - administration & dosage
- T-Lymphocytes - administration & dosage