Acod1 Expression in Cancer Cells Promotes Immune Evasion through the Generation of Inhibitory Peptides.

ABSTRACT: Targeting PD-1 is an important component of many immune checkpoint blockade (ICB) therapeutic approaches. However, ICB is not an efficacious strategy in a variety of cancer types, in part due to immunosuppressive metabolites in the tumor microenvironment (TME). Here, we find that αPD-1-resistant cancer cells produce abundant itaconate (ITA) due to enhanced levels of aconitate decarboxylase (Acod1). Acod1 has an important role in the resistance to αPD-1, as decreasing Acod1 levels in αPD-1 resistant cancer cells can sensitize tumors to αPD-1 therapy. Mechanistically, cancer cells with high Acod1 inhibit the proliferation of naïve CD8⁺ T cells through the secretion of inhibitory factors. Surprisingly, inhibition of CD8⁺ T cell proliferation is not dependent on secretion

SUBMITTER: Schofield JH 

PROVIDER: S-EPMC10515953 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature