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

128 Scopus citations

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

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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  • Cite this

    Tang, H., Wang, Y., Chlewicki, L. K., Zhang, Y., Guo, J., Liang, W., Wang, J., Wang, X., & Fu, Y. X. (2016). Facilitating T Cell Infiltration in Tumor Microenvironment Overcomes Resistance to PD-L1 Blockade. Cancer Cell, 29(3), 285-296. https://doi.org/10.1016/j.ccell.2016.02.004