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.

journal_name

Cancer Cell

journal_title

Cancer cell

authors

Tang H,Wang Y,Chlewicki LK,Zhang Y,Guo J,Liang W,Wang J,Wang X,Fu YX

doi

10.1016/j.ccell.2016.02.004

subject

Has Abstract

pub_date

2016-03-14 00:00:00

pages

285-296

issue

3

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(16)30038-1

journal_volume

29

pub_type

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