Aspirin and immunotherapy: a Faustian bargain?

Area of Science:

• Immunology
• Oncology
• Biochemistry

Background:

• Fibrinogen-like protein 1 (FGL1) is linked to better survival in hepatocellular carcinoma (HCC).
• FGL1 may also induce immune senescence by binding to lymphocyte receptors, potentially hindering antitumor responses.

Purpose of the Study:

• To investigate the mechanism by which aspirin affects FGL1 and its impact on antitumor immunity in HCC.
• To explore the role of sirtuin 2 (SIRT2) in regulating FGL1 acetylation and degradation.

Main Methods:

• The study examined the acetylation of FGL1 by aspirin.
• Researchers assessed the effect of FGL1 degradation on antitumor immunity and HCC survival.
• Inhibitors of sirtuin 2 (SIRT2), a histone deacetylase, were used to validate findings.

Main Results:

• Aspirin treatment leads to FGL1 acetylation and subsequent degradation.
• FGL1 degradation is associated with increased antitumor immunity.
• Inhibition of SIRT2 mimicked the effects of aspirin on FGL1, enhancing antitumor responses and improving survival.

Conclusions:

• Aspirin-mediated acetylation and degradation of FGL1 enhance antitumor immunity and improve survival in HCC.
• SIRT2 plays a role in regulating FGL1 stability and immune response.
• These findings support exploring aspirin and SIRT2 inhibitors as potential immunotherapies for HCC.