PD-L1 and B7-1 Cis-Interaction: New Mechanisms in Immune Checkpoints and Immunotherapies

Christopher D. Nishimura, Marc C. Pulanco, Wei Cui, Liming Lu, Xingxing Zang

Research output: Contribution to journalReview articlepeer-review

15 Scopus citations


Immune checkpoints negatively regulate immune cell responses. Programmed cell death protein 1:programmed death ligand 1 (PD-1:PD-L1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4):B7-1 are among the most important immune checkpoint pathways, and are key targets for immunotherapies that seek to modulate the balance between stimulatory and inhibitory signals to lead to favorable therapeutic outcomes. The current dogma of these two immune checkpoint pathways has regarded them as independent with no interactions. However, the newly characterized PD-L1:B7-1 ligand–ligand cis-interaction and its ability to bind CTLA-4 and CD28, but not PD-1, suggests that these pathways have significant crosstalk. Here, we propose that the PD-L1:B7-1 cis-interaction brings novel mechanistic understanding of these pathways, new insights into mechanisms of current immunotherapies, and fresh ideas to develop better treatments in a variety of therapeutic settings.

Original languageEnglish (US)
Pages (from-to)207-219
Number of pages13
JournalTrends in Molecular Medicine
Issue number3
StatePublished - Mar 2021


  • B7-1
  • CD28
  • CTLA-4
  • PD-1
  • PD-L1
  • cis-interaction
  • immunotherapy

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology


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