Cytokines as an important player in the context of CAR-T cell therapy for cancer: Their role in tumor immunomodulation, manufacture, and clinical implications

CAR-T cell therapies have been recognized as one of the most advanced and efficient strategies to treat patients with hematologic malignancies. However, similar results have not been observed for the treatment of solid tumors. One of the explanations is the fact that tumors have extremely hostile mi...

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Bibliographic Details
Published in:	Frontiers in immunology Vol. 13; p. 947648
Main Authors:	Silveira, Caio Raony Farina, Corveloni, Amanda Cristina, Caruso, Sâmia Rigotto, Macêdo, Nathália Araújo, Brussolo, Natália Moscheta, Haddad, Felipe, Fernandes, Taisa Risque, de Andrade, Pamela Viani, Orellana, Maristela Delgado, Guerino-Cunha, Renato Luiz
Format:	Journal Article
Language:	English
Published:	Frontiers Media S.A 12-09-2022
Subjects:	cancer microenvironment CAR-T cells cell therapy chimeric antigen receptor cytokines Immunology immunomodulation
Online Access:	Get full text
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Summary:	CAR-T cell therapies have been recognized as one of the most advanced and efficient strategies to treat patients with hematologic malignancies. However, similar results have not been observed for the treatment of solid tumors. One of the explanations is the fact that tumors have extremely hostile microenvironments for the infiltration and effector activity of T-cells, mainly due to the presence of highly suppressive cytokines, hypoxia, and reactive oxygen species. Taking advantage of cytokines functionally, new fourth-generation CAR constructs have been developed to target tumor cells and additionally release cytokines that can contribute to the cytotoxicity of T-cells. The manufacturing process, including the use of cytokines in the expansion and differentiation of T cells, is also discussed. Finally, the clinical aspects and the influence of cytokines on the clinical condition of patients, such as cytokine release syndrome, who receive treatment with CAR-T cells are addressed. Therefore, this review aims to highlight how important cytokines are as one of the major players of cell therapy.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1 Edited by: Cleni Mara Marzocchi-Machado, University of São Paulo, Brazil This article was submitted to Cytokines and Soluble Mediators in Immunity, a section of the journal Frontiers in Immunology Reviewed by: Philippe Lewalle, Jules Bordet Institute, Belgium; Saverio Alberti, University of Messina, Italy These authors have contributed equally to this work
ISSN:	1664-3224 1664-3224
DOI:	10.3389/fimmu.2022.947648