Activated SUMOylation restricts the MHC class I antigen presentation pathway to confer immune evasion in cancer
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ABSTRACT: Activated SUMOylation is a hallmark of aggressive cancers. Starting from a targeted screening for SUMO-regulated immune evasion mechanisms, we identified an evolutionary conserved function of activated SUMOylation, which attenuates the immunogenicity of tumor cells. Activated SUMOylation allows cancer cells to evade CD8+ T-cell immunosurveillance by repressing the MHC-I antigen processing and presentation machinery (APM). While loss of the MHC-I APM is a frequent cause of resistance to cancer immunotherapies, the pharmacological inhibition of SUMOylation (SUMOi) restored the expression of the MHC-I APM and enhanced the susceptibility of tumor cells to CD8+ T-cell mediated killing. Importantly, SUMOi also triggered the activation of CD8+ T-cells itself and thereby drives a feed-forward loop amplifying the specific anti-tumor immune response. In summary, we show that activated SUMOylation converts tumor cells into a state of immune evasion, and identify SUMOi as rational therapeutic strategy for enhancing the efficacy of cancer immunotherapies.
INSTRUMENT(S): Orbitrap Fusion Lumos
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): B Cell, Bone Marrow, Blood
DISEASE(S): Lymphoma
SUBMITTER: Paul Hotz
LAB HEAD: Prof. Dr. Stefan Müller
PROVIDER: PXD030506 | Pride | 2022-01-15
REPOSITORIES: Pride
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