{"doi":"10.1172/jci160456","title":"PD-L1 translocation to the plasma membrane enables tumor immune evasion through MIB2 ubiquitination","abstract":"Programmed death-ligand 1 (PD-L1), a critical immune checkpoint ligand, is a transmembrane protein synthesized in the endoplasmic reticulum of tumor cells and transported to the plasma membrane to interact with programmed death 1 (PD-1) expressed on T cell surface. This interaction delivers coinhibitory signals to T cells, thereby suppressing their function and allowing evasion of antitumor immunity. Most companion or complementary diagnostic devices for assessing PD-L1 expression levels in tumor cells used in the clinic or in clinical trials require membranous staining. However, the mechanism driving PD-L1 translocation to the plasma membrane after de novo synthesis is poorly understood. Herein, we showed that mind bomb homolog 2 (MIB2) is required for PD-L1 transportation from the trans-Golgi network (TGN) to the plasma membrane of cancer cells. MIB2 deficiency led to fewer PD-L1 proteins on the tumor cell surface and promoted antitumor immunity in mice. Mechanistically, MIB2 catalyzed nonproteolytic K63-linked ubiquitination of PD-L1, facilitating PD-L1 trafficking through Ras-associated binding 8-mediated (RAB8-mediated) exocytosis from the TGN to the plasma membrane, where it bound PD-1 extrinsically to prevent tumor cell killing by T cells. Our findings demonstrate that nonproteolytic ubiquitination of PD-L1 by MIB2 is required for its transportation to the plasma membrane and tumor cell immune evasion.","journal":"Journal of Clinical Investigation","year":2023,"id":319064,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":58,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9578,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":263249,"name":"Wei Li","orcid":"0000-0001-9931-5990","position":1,"is_corresponding":false},{"id":337595,"name":"Haidan Liu","orcid":"0000-0002-6062-0813","position":2,"is_corresponding":false},{"id":934030,"name":"Xu Wang","orcid":"0000-0001-6920-0375","position":3,"is_corresponding":false},{"id":63736,"name":"Cristian Coarfa","orcid":"0000-0002-4183-4939","position":4,"is_corresponding":false},{"id":363,"name":"Chao Cheng","orcid":"0000-0002-5002-3417","position":5,"is_corresponding":false},{"id":1027200,"name":"Xinlian Yu","orcid":"0000-0001-8418-4377","position":6,"is_corresponding":false},{"id":647223,"name":"Zhaoyang Zeng","orcid":null,"position":7,"is_corresponding":false},{"id":134903,"name":"Ya Cao","orcid":"0000-0002-3558-3336","position":8,"is_corresponding":false},{"id":288535,"name":"Ken H. Young","orcid":"0000-0002-5755-8932","position":9,"is_corresponding":false},{"id":288537,"name":"Yong Li","orcid":"0000-0001-8838-1714","position":10,"is_corresponding":false},{"id":288530,"name":"Xinfang Yu","orcid":"0000-0003-3738-7133","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-19T01:07:06.454099Z","pmid":"36719382","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}