IFN-γ and CD38 in Hyperprogressive Cancer Development

Angelicola, Stefania and Ruzzi, Francesca and Landuzzi, Lorena and Scalambra, Laura and Gelsomino, Francesco and Ardizzoni, Andrea and Nanni, Patrizia and Lollini, Pier-Luigi and Palladini, Arianna (2021) IFN-γ and CD38 in Hyperprogressive Cancer Development. Cancers, 13 (2). p. 309. ISSN 2072-6694

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Abstract

Immune checkpoint inhibitors (ICIs) improve the survival of patients with multiple types of cancer. However, low response rates and atypical responses limit their success in clinical applications. The paradoxical acceleration of tumor growth after treatment, defined as hyperprogressive disease (HPD), is the most difficult problem facing clinicians and patients alike. The mechanisms that underlie hyperprogression (HP) are still unclear and controversial, although different factors are associated with the phenomenon. In this review, we propose two factors that have not yet been demonstrated to be directly associated with HP, but upon which it is important to focus attention. IFN-γ is a key cytokine in antitumor response and its levels increase during ICI therapy, whereas CD38 is an alternative immune checkpoint that is involved in immunosuppressive responses. As both factors are associated with resistance to ICI therapy, we have discussed their possible involvement in HPD with the conclusion that IFN-γ may contribute to HP onset through the activation of the inflammasome pathway, immunosuppressive enzyme IDO1 and activation-induced cell death (AICD) in effector T cells, while the role of CD38 in HP may be associated with the activation of adenosine receptors, hypoxia pathways and AICD-dependent T-cell depletion.

Item Type: Article
Subjects: Journal Eprints > Medical Science
Depositing User: Managing Editor
Date Deposited: 19 Jan 2023 10:14
Last Modified: 06 Jul 2024 06:32
URI: http://repository.journal4submission.com/id/eprint/716

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