{"doi":"10.1172/jci153454","title":"An Asia-specific variant of human IgG1 represses colorectal tumorigenesis by shaping the tumor microenvironment","abstract":"Emerging studies have focused on ways to treat cancers by modulating T cell activation. However, whether B cell receptor signaling in the tumor microenvironment (TME) can be harnessed for immunotherapy is unclear. Here, we report that an Asia-specific variant of human IgG1 containing a Gly396 to Arg396 substitution (hIgG1-G396R) conferred improved survival of patients with colorectal cancer (CRC). Mice with knockin of the murine functional homolog mIgG2c-G400R recapitulated the alleviated tumorigenesis and progression in murine colon carcinoma models. Immune profiling of the TME revealed broad mobilizations of IgG1+ plasma cells, CD8+ T cells, CD103+ DCs, and active tertiary lymphoid structure formation, suggesting an effective antitumor microenvironment in hIgG1-G396R CRC patients. Mechanistically, this variant potentiated tumor-associated antigen-specific (TAA-specific) plasma cell differentiation and thus antibody production. These elevated TAA-specific IgG2c antibodies in turn efficiently boosted the antibody-dependent tumor cell phagocytosis and TAA presentation to effector CD8+ T cells. Notably, adoptive transfer of TAA-specific class-switched memory B cells harboring this variant exhibited therapeutic efficacy in murine tumor models, indicating their clinical potential. All these results prompted a prospective investigation of hIgG1-G396R in patients with CRC as a biomarker for clinical prognosis and demonstrated that manipulating the functionality of IgG1+ memory B cells in tumors could improve immunotherapy outcomes.","journal":"Journal of Clinical Investigation","year":2022,"id":240631,"datarank":0.5709993734655481,"base_score":3.8066624897703196,"endowment":3.8066624897703196,"self_citation_contribution":0.5709993734655481,"citation_network_contribution":0.0,"self_endowment_contribution":0.5709993734655481,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":44,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9547,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":617592,"name":"Zhen Zhang","orcid":"0000-0003-4657-0589","position":1,"is_corresponding":false},{"id":121394,"name":"Xiangjun Chen","orcid":null,"position":2,"is_corresponding":false},{"id":869284,"name":"Xu-Yan Wang","orcid":null,"position":3,"is_corresponding":false},{"id":868669,"name":"Shishang Qin","orcid":"0000-0003-0324-5073","position":4,"is_corresponding":false},{"id":869285,"name":"Liaoqi Du","orcid":null,"position":5,"is_corresponding":false},{"id":869286,"name":"Changjiang Yang","orcid":null,"position":6,"is_corresponding":false},{"id":869287,"name":"Liyu Zhu","orcid":null,"position":7,"is_corresponding":false},{"id":211196,"name":"Wenbo Sun","orcid":null,"position":8,"is_corresponding":false},{"id":869288,"name":"Yongjie Zhu","orcid":null,"position":9,"is_corresponding":false},{"id":869289,"name":"Qinwen Zheng","orcid":null,"position":10,"is_corresponding":false},{"id":869290,"name":"Shidong Zhao","orcid":null,"position":11,"is_corresponding":false},{"id":868670,"name":"Quan Wang","orcid":"0000-0002-2821-5017","position":12,"is_corresponding":false},{"id":868671,"name":"Long Zhao","orcid":"0000-0002-9014-8345","position":13,"is_corresponding":false},{"id":869291,"name":"Yilin Lin","orcid":null,"position":14,"is_corresponding":false},{"id":520382,"name":"Jinghe Huang","orcid":"0000-0002-1968-871X","position":15,"is_corresponding":false},{"id":39958,"name":"Fan Wu","orcid":"0000-0003-4741-3948","position":16,"is_corresponding":false},{"id":237956,"name":"Lu Lu","orcid":"0000-0002-2255-0391","position":17,"is_corresponding":false},{"id":51129,"name":"Fei Wang","orcid":"0000-0001-6712-3468","position":18,"is_corresponding":false},{"id":868672,"name":"Wenjie Zheng","orcid":"0000-0002-3165-8185","position":19,"is_corresponding":false},{"id":869292,"name":"Xiao-Hua Zhou","orcid":null,"position":20,"is_corresponding":false},{"id":869293,"name":"Xiaozhen Zhao","orcid":null,"position":21,"is_corresponding":false},{"id":869294,"name":"Ziye Wang","orcid":null,"position":22,"is_corresponding":false},{"id":869295,"name":"Sun Xiao-Lin","orcid":null,"position":23,"is_corresponding":false},{"id":869296,"name":"Yingjiang Ye","orcid":null,"position":24,"is_corresponding":false},{"id":376120,"name":"Shan Wang","orcid":"0000-0001-8292-5717","position":25,"is_corresponding":false},{"id":477188,"name":"Zhanguo Li","orcid":"0000-0002-2590-6242","position":26,"is_corresponding":false},{"id":868673,"name":"Hai Qi","orcid":"0000-0001-5475-3989","position":27,"is_corresponding":false},{"id":14284,"name":"Zemin Zhang","orcid":"0000-0003-3789-6536","position":28,"is_corresponding":false},{"id":868674,"name":"Dong-Ming Kuang","orcid":"0000-0003-3570-9717","position":29,"is_corresponding":false},{"id":868675,"name":"Lei Zhang","orcid":"0000-0001-5589-5380","position":30,"is_corresponding":false},{"id":869297,"name":"Zhanlong Shen","orcid":null,"position":31,"is_corresponding":false},{"id":713390,"name":"Wanli Liu","orcid":"0000-0003-2624-6802","position":32,"is_corresponding":false},{"id":111521,"name":"Bing Yang","orcid":null,"position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:22:51.435773Z","pmid":"35133976","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":[]}