Parkin activation suppresses antigen presentation of macrophages to promote tumour progression

Here, through a series of in vivo murine tumour progression models, we found that Parkin deficiency inhibit the progression of multiple cancers. scRNA-seq analyses were performed on tumour-infiltrating CD45+ cells sorting from MC38 tumours in WT or Park2-/- mice. scRNA-seq and flow cytometry analyses profiled distinct anti-tumour macrophage subsets and effector T cell subsets in the tumor immune microenvironment of Park2-/- mice, which were further validated by adoptive transfer assays. Mechanistically, Parkin deficiency facilitates MHC-I expression on TAMs through an unconventional AMPK-dependent pathway, thereby yielding antigen-specific T-cell activation and persistent tumoricidal effects. In addition, we found that Park2-/- TAMs-related signature was associated with improved prognosis in solid tumour patients. Our findings underscore Parkin as a negative immune regulator confining intercellular crosstalk between macrophages and T cells that underpins tumour immune evasion, reinforcing Parkin as a promising target for optimizing tumour immunotherapy. scRNA-seq analyses were performed on tumour-infiltrating CD45+ cells sorting from MC38 tumours in WT or Park2-/- mice.