A study of IL-1β-Associated NNT Acetylation Orchestrates Iron–sulfur Cluster Maintenance and Cancer Immunotherapy Resistance. Han et al

Published: 26 May 2023| Version 2 | DOI: 10.17632/bz4754xbwm.2
Yi Han, Rui-hua Xu, Huai-qiang Ju


Interleukin-1β (IL-1β) is a key protein in inflammation and contributes to tumor progression. However, the role of IL-1β in cancer is ambiguous or even contradictory due to its pro- and antitumor potential. Here, we found that upon IL-1β stimulation, nicotinamide nucleotide transhydrogenase (NNT) in cancer cells is acetylated at lysine (K) 1042 (NNT K1042ac) and thereby induces the mitochondrial translocation of p300/CBP-associated factor (PCAF). This acetylation enhances NNT activity by increasing the binding affinity of NNT for NADP+ and therefore boosts NADPH production, which subsequently sustains sufficient iron–sulfur cluster maintenance and protects tumor cells from ferroptosis. Abrogating NNT K1042 acetylation dramatically attenuates IL-1β-promoted tumor immune evasion and synergizes with PD-1 blockade. In addition, NNT K1042ac is associated with IL-1β expression and the prognosis of human gastric cancer. Our findings demonstrate a novel mechanism of IL-1β-promoted tumor immune evasion through which tumor cell metabolism is regulated, implicating the therapeutic potential of disrupting the link between IL-1β and tumor cells by inhibiting NNT acetylation. This is the original data set for the study that contains all of the unprocessed microscopy images, gels, western blots used in this study.



Sun Yat-sen University Cancer Center


Acetylation, Immunotherapy, Interleukin-1