Targeting B7-H1 (PD-L1) sensitizes cancer cells to chemotherapy

Xiaosheng Wu, Yanli Li, Xin Liu, Chunhua Chen, Susan M. Harrington, Siyu Cao, Tiancheng Xie, Amanda Orzechowski, Tu Pham, Aaron S. Mansfield, Yiyi Yan, Eugene D. Kwon, Liewei Wang, Kun Ling, Haidong Dong

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Development of resistance to chemotherapy is a major obstacle in extending the survival of patients with cancer. Although originally defined as an immune checkpoint molecule, B7-H1 (also named as PD-L1 or CD274) was found to play a role in cancer chemoresistance; however, the underlying mechanism of action of B7-H1 in regulation of chemotherapy sensitivity remains unclear in cancer cells. Here we show that development of chemoresistance depends on an increased activation of ERK in cancer cells overexpressing B7-H1. Conversely, B7-H1 knockout (KO) by CRISPR/Cas9 renders human cancer cells susceptible to chemotherapy in a cell-context dependent manner through a reduced activation of p38 MAPK. B7-H1 was found to associate with the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) and this association promoted or maintained the activation of ERK or p38 MAPK in cancer cells. Importantly, we found that targeting B7-H1 by anti-B7-H1 monoclonal antibody (H1A) increased the sensitivity of human triple negative breast cancer cells to cisplatin therapy in vivo. Our results suggest that targeting B7-H1 by an antibody capable of disrupting B7-H1 signals may be a new approach to sensitize cancer cells to chemotherapy.

Original languageEnglish (US)
Article numbere01039
Issue number12
StatePublished - Dec 2018


  • Cancer research
  • Oncology

ASJC Scopus subject areas

  • General


Dive into the research topics of 'Targeting B7-H1 (PD-L1) sensitizes cancer cells to chemotherapy'. Together they form a unique fingerprint.

Cite this