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 toCD28/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.

Sconocchia, G., Lanzilli, G., Cesarini, V., Silvestris, D.a., Rezvani, K., Arriga, R., et al. (2022). Direct CD32 T-cell cytotoxicity: implications for breast cancer prognosis and treatment. LIFE SCIENCE ALLIANCE, 5(12), 1-16 [10.26508/lsa.202201590].

Direct CD32 T-cell cytotoxicity: implications for breast cancer prognosis and treatment

Cesarini, Valeriana;Caratelli, Sara;Irno Consalvo, Maria;Buccisano, Francesco;del Principe, Maria I;Venditti, Adriano;Ottaviani, Alessio;
2022-10-14

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 toCD28/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.
14-ott-2022
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/15 - MALATTIE DEL SANGUE
English
Con Impact Factor ISI
Investigator Grants 2015-17120, Italian Association for Cancer Research (AIRC) Investigator Grants 2020-24440, and European Union, European Fund for Regional Development, MUR-PON: Unit IFT, Grant TITAN 2021- ARS01_00906 to G Sconocchia.
Sconocchia, G., Lanzilli, G., Cesarini, V., Silvestris, D.a., Rezvani, K., Arriga, R., et al. (2022). Direct CD32 T-cell cytotoxicity: implications for breast cancer prognosis and treatment. LIFE SCIENCE ALLIANCE, 5(12), 1-16 [10.26508/lsa.202201590].
Sconocchia, G; Lanzilli, G; Cesarini, V; Silvestris, Da; Rezvani, K; Arriga, R; Caratelli, S; Chen, K; Dou, J; Cenciarelli, C; Toietta, G; Baldari, S;...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/307175
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