title: CD137-CRDI is not necessary in the role of contacting its natural ligand.
abstract: Immune checkpoint inhibitors result in impressive clinical responses and are expanding to treat a wide variety of tumors. One common problem is low responses from current clinical trials that only benefit a fraction of patients. One key promising direction is combination therapy to increase clinical benefit. CD137, a well-defined antitumor target, can cause strong co-stimulating activity and break immune tolerance. In this study, the role of CD137-CRDI (cysteine rich domain I) in the binding of CD137-CD137L was further investigated based on our previous work. The results revealed that CRDI-mediated limited CD137 assembly without relying on CD137L. Furthermore, CRDI was not involved in direct contact with CD137L in either mice or humans. Isolated mouse CRDII and human CRDII+CRDIII were proven to be the minimum unit for interface with their respective ligands. Fine-tuning of this signaling may improve CD137-targeting strategy.
authors.affiliation: Department of Central Laboratory, Beijing Chest Hospital, Capital Medical University and Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: Yi
authors.affiliation: Department of Central Laboratory, Beijing Chest Hospital, Capital Medical University and Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People's Republic of China.
authors.forename: Zhuohong
authors.initials: Z
authors.lastname: Yan
authors.affiliation: Beijing Key Laboratory for Drug Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University and Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People's Republic of China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Jia
authors.affiliation: Department of Central Laboratory, Beijing Chest Hospital, Capital Medical University and Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People's Republic of China.
authors.forename: Xiaojue
authors.initials: X
authors.lastname: Wang
authors.affiliation: Chinese Center for Disease Control and Prevention, Beijing, People's Republic of China.
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Central Laboratory, Beijing Chest Hospital, Capital Medical University and Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People's Republic of China.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Zhang
mesh_terms: D053330:4-1BB Ligand / Q000378:metabolism*; D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D006801:Humans; D007700:Kinetics; D008024:Ligands; D051379:Mice; D058105:Polymerization; D011485:Protein Binding; D011487:Protein Conformation; D000072417:Protein Domains; D017384:Sequence Deletion; D013329:Structure-Activity Relationship; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D053330:4-1BB Ligand; D008024:Ligands; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9