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

Haidong Tang, Yang Wang, Lukasz K. Chlewicki, Yuan Zhang, Jingya Guo, Wei Liang, Jieyi Wang, Xiaoxiao Wang, Yang Xin Fu

Research output: Contribution to journalArticle

107 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)285-296
Number of pages12
JournalCancer Cell
Volume29
Issue number3
DOIs
StatePublished - Mar 14 2016

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Tumor Microenvironment
T-Lymphocytes
Neoplasms
Light
Neoplasm Antibodies
Cellular Microenvironment
Lymphotoxin-alpha
Chemokines
Immunotherapy
Tumor Necrosis Factor-alpha

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Facilitating T Cell Infiltration in Tumor Microenvironment Overcomes Resistance to PD-L1 Blockade. / Tang, Haidong; Wang, Yang; Chlewicki, Lukasz K.; Zhang, Yuan; Guo, Jingya; Liang, Wei; Wang, Jieyi; Wang, Xiaoxiao; Fu, Yang Xin.

In: Cancer Cell, Vol. 29, No. 3, 14.03.2016, p. 285-296.

Research output: Contribution to journalArticle

Tang, H, Wang, Y, Chlewicki, LK, Zhang, Y, Guo, J, Liang, W, Wang, J, Wang, X & Fu, YX 2016, 'Facilitating T Cell Infiltration in Tumor Microenvironment Overcomes Resistance to PD-L1 Blockade', Cancer Cell, vol. 29, no. 3, pp. 285-296. https://doi.org/10.1016/j.ccell.2016.02.004
Tang, Haidong ; Wang, Yang ; Chlewicki, Lukasz K. ; Zhang, Yuan ; Guo, Jingya ; Liang, Wei ; Wang, Jieyi ; Wang, Xiaoxiao ; Fu, Yang Xin. / Facilitating T Cell Infiltration in Tumor Microenvironment Overcomes Resistance to PD-L1 Blockade. In: Cancer Cell. 2016 ; Vol. 29, No. 3. pp. 285-296.
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