Blinatumomab differentially modulates peripheral blood and bone marrow immune cell repertoire: a Campus ALL study

Ocadlikova, D, Lussana, F, Fracchiolla, N, Bonifacio, M, Santoro, L, Delia, M, Chiaretti, S, Pasciolla, C, Cignetti, A, Forghieri, F, Grimaldi, F, Corradi, G, Zannoni, L, De Propris, S, Borleri, GM, Tanasi, I, Vadakekolathu, J ORCID: https://orcid.org/0000-0002-2671-4285, Rutella, S ORCID: https://orcid.org/0000-0003-1970-7375, Guarini, AR, Foà, R, Curti, A and the Campus ALL, 2023. Blinatumomab differentially modulates peripheral blood and bone marrow immune cell repertoire: a Campus ALL study. British Journal of Haematology. ISSN 0007-1048

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Abstract

Blinatumomab is the first bi-specific T-cell engager approved for relapsed or refractory B-cell precursor acute lymphoblastic leukaemia (B-ALL). Despite remarkable clinical results, the effects of blinatumomab on the host immune cell repertoire are not fully elucidated. In the present study, we characterized the peripheral blood (PB) and, for the first time, the bone marrow (BM) immune cell repertoire upon blinatumomab treatment. Twenty-nine patients with B-ALL received blinatumomab according to clinical practice. Deep multiparametric flow cytometry was used to characterize lymphoid subsets during the first treatment cycle. Blinatumomab induced a transient redistribution of PB effector T-cell subsets and Treg cells with a persistent increase in cytotoxic NK cells, which was associated with a transient upregulation of immune checkpoint receptors on PB CD4 and CD8 T-cell subpopulations and of CD39 expression on suppressive Treg cells. Of note, BM immune T-cell subsets showed a broader post-treatment subversion, including the modulation of markers associated with a T-cell-exhausted phenotype. In conclusion, our study indicates that blinatumomab differentially modulates the PB and BM immune cell repertoire, which may have relevant clinical implications in the therapeutic setting.

Item Type:	Journal article
Publication Title:	British Journal of Haematology
Creators:	Ocadlikova, D., Lussana, F., Fracchiolla, N., Bonifacio, M., Santoro, L., Delia, M., Chiaretti, S., Pasciolla, C., Cignetti, A., Forghieri, F., Grimaldi, F., Corradi, G., Zannoni, L., De Propris, S., Borleri, G.M., Tanasi, I., Vadakekolathu, J., Rutella, S., Guarini, A.R., Foà, R., Curti, A. and the Campus ALL
Publisher:	Wiley
Date:	12 September 2023
ISSN:	0007-1048
Identifiers:	Number Type 10.1111/bjh.19104 DOI 1803987 Other
Rights:	© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Divisions:	Schools > School of Science and Technology
Record created by:	Laura Ward
Date Added:	13 Sep 2023 08:40
Last Modified:	13 Sep 2023 08:40
URI:	https://irep.ntu.ac.uk/id/eprint/49691

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