Involvement of the ubiquitin-proteasome system in the regulation of the tumor microenvironment and progression.

PD-1 and its ligands PD-L1 or PD-L2 play an extremely significant role in regulating tumor progression. 75 Aberrant ubiquitination and deubiquitination of this checkpoint affect checkpoint-mediated immune activity. 76 F-box only proteins 38 (FBXO38) is a PD-1-specific E3 ligase and mediates polyubiquitination of the K233 site on PD-1, thereby reducing PD-1 expression on the T cell surface and blocking PD-1/PD-L1 axis-mediated immunosuppression ( Fig. 3 ).

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