title: Facilitating T Cell Infiltration in Tumor Microenvironment Overcomes Resistance to PD-L1 Blockade.
abstract: Immune checkpoint blockade therapies fail to induce responses in the majority of cancer patients, so how to increase the objective response rate becomes an urgent challenge. Here, we demonstrate that sufficient T cell infiltration in tumor tissues is a prerequisite for response to PD-L1 blockade. Targeting tumors with tumor necrosis factor superfamily member LIGHT activates lymphotoxin β-receptor signaling, leading to the production of chemokines that recruit massive numbers of T cells. Furthermore, targeting non-T cell-inflamed tumor tissues by antibody-guided LIGHT creates a T cell-inflamed microenvironment and overcomes tumor resistance to checkpoint blockade. Our data indicate that targeting LIGHT might be a potent strategy to increase the responses to checkpoint blockades and other immunotherapies in non-T cell-inflamed tumors.
authors.affiliation: Department of Pathology and Committee on Immunology, University of Chicago, Chicago, IL 60637, USA; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA.
authors.forename: Haidong
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Pathology and Committee on Immunology, University of Chicago, Chicago, IL 60637, USA; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology and Committee on Immunology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Lukasz K
authors.initials: LK
authors.lastname: Chlewicki
authors.affiliation: Department of Pathology and Committee on Immunology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Chinese Academy of Science Key Laboratory for Infection and Immunity, IBP-UTSW Joint Immunotherapy Group, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jingya
authors.initials: J
authors.lastname: Guo
authors.affiliation: Chinese Academy of Science Key Laboratory for Infection and Immunity, IBP-UTSW Joint Immunotherapy Group, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liang
authors.affiliation: Oncology Biologics, AbbVie Biotherapeutics Research (ABR), 1500 Seaport Boulevard, Redwood City, CA 94063, USA.
authors.forename: Jieyi
authors.initials: J
authors.lastname: Wang
authors.affiliation: Alphamab Co. Ltd., Suzhou, Jiangsu 215125, China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA; Chinese Academy of Science Key Laboratory for Infection and Immunity, IBP-UTSW Joint Immunotherapy Group, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: yang-xin.fu@utsouthwestern.edu.
authors.forename: Yang-Xin
authors.initials: YX
authors.lastname: Fu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000276:immunology*; D060890:B7-H1 Antigen / Q000276:immunology*; D019008:Drug Resistance, Neoplasm / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D053259:Lymphotoxin beta Receptor / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D059016:Tumor Microenvironment / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; D053259:Lymphotoxin beta Receptor; D014409:Tumor Necrosis Factor-alpha