{"entity": "journal", "iuid": "3094366bf0f2422dacf06f8b9c009d5e", "timestamp": "2026-08-23T09:28:37.866Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/journal/Sci%20Bull%20%28Beijing%29.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/journal/Sci%20Bull%20%28Beijing%29"}}, "title": "Sci Bull (Beijing)", "issn": "2095-9281", "issn-l": null, "publications_count": 1, "publications": [{"entity": "publication", "iuid": "2c7eac36916040fd8280eee941dd55f7", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/2c7eac36916040fd8280eee941dd55f7.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/2c7eac36916040fd8280eee941dd55f7"}}, "title": "Modulator of TMB-associated immune infiltration (MOTIF) predicts immunotherapy response and guides combination therapy.", "authors": [{"family": "Qian", "given": "Zheng-Yu", "initials": "ZY"}, {"family": "Pan", "given": "Yi-Qian", "initials": "YQ"}, {"family": "Li", "given": "Xue-Xin", "initials": "XX"}, {"family": "Chen", "given": "Yan-Xing", "initials": "YX"}, {"family": "Wu", "given": "Hao-Xiang", "initials": "HX"}, {"family": "Liu", "given": "Ze-Xian", "initials": "ZX"}, {"family": "Kosar", "given": "Martin", "initials": "M"}, {"family": "Bartek", "given": "Jiri", "initials": "J"}, {"family": "Wang", "given": "Zi-Xian", "initials": "ZX"}, {"family": "Xu", "given": "Rui-Hua", "initials": "RH"}], "type": "journal article", "published": "2024-03-30", "journal": {"title": "Sci Bull (Beijing)", "issn": "2095-9281", "volume": "69", "issue": "6", "pages": "803-822", "issn-l": null}, "abstract": "Patients with high tumor mutational burden (TMB) levels do not consistently respond to immune checkpoint inhibitors (ICIs), possibly because a high TMB level does not necessarily result in adequate infiltration of CD8+ T cells. Using bulk ribonucleic acid sequencing (RNA-seq) data from 9311 tumor samples across 30 cancer types, we developed a novel tool called the modulator of TMB-associated immune infiltration (MOTIF), which comprises genes that can determine the extent of CD8+ T cell infiltration prompted by a certain TMB level. We confirmed that MOTIF can accurately reflect the integrity and defects of the cancer-immunity cycle. By analyzing 84 human single-cell RNA-seq datasets from 32 types of solid tumors, we revealed that MOTIF can provide insights into the diverse roles of various cell types in the modulation of CD8+ T cell infiltration. Using pretreatment RNA-seq data from 13 ICI-treated cohorts, we validated the use of MOTIF in predicting CD8+ T cell infiltration and ICI efficacy. Among the components of MOTIF, we identified EMC3 as a negative regulator of CD8+ T cell infiltration, which was validated via in vivo studies. Additionally, MOTIF provided guidance for the potential combinations of programmed death 1 blockade with certain immunostimulatory drugs to facilitate CD8+ T cell infiltration and improve ICI efficacy.", "doi": "10.1016/j.scib.2024.01.025", "pmid": "38320897", "labels": [], "xrefs": [{"db": "pii", "key": "S2095-9273(24)00043-4"}], "notes": [], "created": "2026-08-20T08:04:30.737Z", "modified": "2026-08-20T08:04:30.776Z"}], "created": "2026-08-20T08:04:30.745Z", "modified": "2026-08-20T08:04:30.745Z"}