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Cancer Cell. 2016 Mar 14;29(3):285-296. doi: 10.1016/j.ccell.2016.02.004.

Facilitating T Cell Infiltration in Tumor Microenvironment Overcomes Resistance to PD-L1 Blockade.

Author information

1
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.
2
Department of Pathology and Committee on Immunology, University of Chicago, Chicago, IL 60637, USA.
3
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.
4
Oncology Biologics, AbbVie Biotherapeutics Research (ABR), 1500 Seaport Boulevard, Redwood City, CA 94063, USA.
5
Alphamab Co. Ltd., Suzhou, Jiangsu 215125, China.
6
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.

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.

PMID:
26977880
PMCID:
PMC4794755
DOI:
10.1016/j.ccell.2016.02.004
[Indexed for MEDLINE]
Free PMC Article

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