TY - JOUR
T1 - IFN-γ and CD38 in Hyperprogressive Cancer Development
AU - Angelicola, Stefania
AU - Ruzzi, Francesca
AU - Landuzzi, Lorena
AU - Scalambra, Laura
AU - Gelsomino, Francesco
AU - Ardizzoni, Andrea
AU - Nanni, Patrizia
AU - Lollini, Pier-Luigi
AU - Palladini, Arianna
PY - 2021/1/15
Y1 - 2021/1/15
N2 - 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.
AB - 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.
KW - CD38
KW - IFN-γ
KW - cancer
KW - hyperprogression
KW - hyperprogressive disease
KW - immune checkpoint inhibitors
KW - immunotherapy
KW - macrophage
KW - tumor microenvironment
U2 - 10.3390/cancers13020309
DO - 10.3390/cancers13020309
M3 - Review article
C2 - 33467713
VL - 13
SP - 1
EP - 24
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 2
ER -