Cell Res：卞修武院士等揭示PD-L1在癌症免疫逃逸中的全新功能——诱导β2m泛素化和降解，实现癌细胞免疫逃逸

Core Viewpoint - The article discusses the significant therapeutic effects of PD-1/PD-L1 immune checkpoint blockade therapies across various cancer types, while highlighting the challenge of resistance mechanisms that limit their clinical efficacy [2]. Group 1: Research Findings - A study published in Cell Research reveals that tumor PD-L1 induces β2m ubiquitylation and degradation, facilitating immune evasion by cancer cells [3]. - This research uncovers a novel function of PD-L1 in immune evasion, expanding the understanding of intrinsic resistance mechanisms to immune checkpoint blockade therapies [8]. Group 2: Mechanism of Resistance - β2-microglobulin (β2m) is essential for the stability and surface expression of MHC-I molecules in tumor cells. Defects in the B2M gene can reduce MHC-I levels, weakening CD8+ T cell recognition and leading to resistance against PD-1/PD-L1 therapies [6]. - The study found that PD-L1 possesses E3 ubiquitin ligase activity, which induces β2m ubiquitylation and subsequent degradation, significantly lowering MHC-I levels on tumor and antigen-presenting cells [6]. - This mechanism allows tumor cells to evade recognition by CD8+ T cells, resulting in resistance to PD-1/PD-L1 therapies, particularly in tumors with low baseline β2m expression [6].