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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antineoplastic Agents / immunology*
  • B7-H1 Antigen / immunology*
  • Drug Resistance, Neoplasm / immunology
  • Humans
  • Immunotherapy / methods
  • Lymphotoxin beta Receptor / immunology
  • Mice
  • Mice, Inbred C57BL
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / immunology*
  • Tumor Necrosis Factor-alpha / immunology


  • Antineoplastic Agents
  • B7-H1 Antigen
  • Lymphotoxin beta Receptor
  • Tumor Necrosis Factor-alpha