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

Giuseppe Sconocchia; Giulia Lanzilli; Valeriana Cesarini; Domenico A. Silvestris; Katayoun Rezvani; Roberto Arriga; Sara Caratelli; Ken Chen; Jinzhuang Dou; Carlo Cenciarelli; Gabriele Toietta; Silvia Baldari; Tommaso Sconocchia; Francesca De Paolis; Anna Aureli; Giandomenica Iezzi; Maria Irno Consalvo; Francesco Buccisano; Maria I. del Principe; Luca Maurillo; Adriano Venditti; Alessio Ottaviani; Giulio C. Spagnoli

doi:10.26508/lsa.202201590

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

Giuseppe Sconocchia, Giulia Lanzilli, Valeriana Cesarini, Domenico A. Silvestris, Katayoun Rezvani, Roberto Arriga, Sara Caratelli, Ken Chen, Jinzhuang Dou, Carlo Cenciarelli, Gabriele Toietta, Silvia Baldari, Tommaso Sconocchia, Francesca De Paolis, Anna Aureli, Giandomenica Iezzi, Maria Irno Consalvo, Francesco Buccisano, Maria I. del Principe, Luca MaurilloAdriano Venditti, Alessio Ottaviani, Giulio C. Spagnoli

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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.

Original language	English (US)
Article number	e202201590
Journal	Life science alliance
Volume	5
Issue number	12
DOIs	https://doi.org/10.26508/lsa.202201590
State	Published - Dec 2022

ASJC Scopus subject areas

Ecology
Biochemistry, Genetics and Molecular Biology (miscellaneous)
Plant Science
Health, Toxicology and Mutagenesis

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Sconocchia, G., Lanzilli, G., Cesarini, V., Silvestris, D. A., 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., Consalvo, M. I., Buccisano, F., del Principe, M. I., ... Spagnoli, G. C. (2022). Direct CD32 T-cell cytotoxicity: implications for breast cancer prognosis and treatment. Life science alliance, 5(12), Article e202201590. https://doi.org/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, Sconocchia, T, De Paolis, F, Aureli, A, Iezzi, G, Consalvo, MI, Buccisano, F, del Principe, MI, Maurillo, L, Venditti, A, Ottaviani, A & Spagnoli, GC 2022, 'Direct CD32 T-cell cytotoxicity: implications for breast cancer prognosis and treatment', Life science alliance, vol. 5, no. 12, e202201590. https://doi.org/10.26508/lsa.202201590

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title = "Direct CD32 T-cell cytotoxicity: implications for breast cancer prognosis and treatment",

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.",

author = "Giuseppe Sconocchia and Giulia Lanzilli and Valeriana Cesarini and Silvestris, {Domenico A.} and Katayoun Rezvani and Roberto Arriga and Sara Caratelli and Ken Chen and Jinzhuang Dou and Carlo Cenciarelli and Gabriele Toietta and Silvia Baldari and Tommaso Sconocchia and {De Paolis}, Francesca and Anna Aureli and Giandomenica Iezzi and Consalvo, {Maria Irno} and Francesco Buccisano and {del Principe}, {Maria I.} and Luca Maurillo and Adriano Venditti and Alessio Ottaviani and Spagnoli, {Giulio C.}",

note = "Publisher Copyright: {\textcopyright} 2022 Sconocchia et al.",

year = "2022",

month = dec,

doi = "10.26508/lsa.202201590",

language = "English (US)",

volume = "5",

journal = "Life science alliance",

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T2 - implications for breast cancer prognosis and treatment

AU - Sconocchia, Giuseppe

AU - Lanzilli, Giulia

AU - Cesarini, Valeriana

AU - Silvestris, Domenico A.

AU - Rezvani, Katayoun

AU - Arriga, Roberto

AU - Caratelli, Sara

AU - Chen, Ken

AU - Dou, Jinzhuang

AU - Cenciarelli, Carlo

AU - Toietta, Gabriele

AU - Baldari, Silvia

AU - Sconocchia, Tommaso

AU - De Paolis, Francesca

AU - Aureli, Anna

AU - Iezzi, Giandomenica

AU - Consalvo, Maria Irno

AU - Buccisano, Francesco

AU - del Principe, Maria I.

AU - Maurillo, Luca

AU - Venditti, Adriano

AU - Ottaviani, Alessio

AU - Spagnoli, Giulio C.

PY - 2022/12

Y1 - 2022/12

N2 - 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.

AB - 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.

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

Abstract

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