CD8A and neoplasm: In addition to increase the expression of immune checkpoint ligands, defects in MHC-I-mediated antigen processing and presentation (APP) can directly hinder the tumor recognition of CD8 + T cells and restrain their activation and proliferation.37 Genetic mutations in essential genes involved in MHC-I APP have been implicated in tumor progression and the development of resistance to ICB therapy.13,38 Therefore, beyond interpreting the regulation of PD-L1 pathway, it is also crucial to understand the regulatory mechanisms of MHC-I in tumor cells.