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Blockade of PD-1, PD-L1, and TIM-3 Altered Distinct Immune- and Cancer-Related Signaling Pathways in the Transcriptome of Human Breast Cancer Explants

journal contribution
submitted on 2024-05-19, 09:33 and posted on 2024-05-19, 12:48 authored by Reem Saleh, Salman M. Toor, Dana Al-Ali, Varun Sasidharan Nair, Eyad Elkord

Immune checkpoint inhibitors (ICIs) are yet to have a major advantage over conventional therapies, as only a fraction of patients benefit from the currently approved ICIs and their response rates remain low. We investigated the effects of different ICIs—anti-programmed cell death protein 1 (PD-1), anti-programmed death ligand-1 (PD-L1), and anti-T cell immunoglobulin and mucin-domain containing-3 (TIM-3)—on human primary breast cancer explant cultures using RNA-Seq. Transcriptomic data revealed that PD-1, PD-L1, and TIM-3 blockade follow unique mechanisms by upregulating or downregulating distinct pathways, but they collectively enhance immune responses and suppress cancer-related pathways to exert anti-tumorigenic effects. We also found that these ICIs upregulated the expression of other IC genes, suggesting that blocking one IC can upregulate alternative ICs, potentially giving rise to compensatory mechanisms by which tumor cells evade anti-tumor immunity. Overall, the transcriptomic data revealed some unique mechanisms of the action of monoclonal antibodies (mAbs) targeting PD-1, PD-L1, and TIM-3 in human breast cancer explants. However, further investigations and functional studies are warranted to validate these findings.

Other Information

Published in: Genes

See article on publisher's website:



  • English



Publication Year

  • 2020

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License.

Institution affiliated with

  • Hamad Bin Khalifa University
  • Qatar Biomedical Research Institute - HBKU
  • Cancer Research Center - QBRI
  • Weill Cornell Medicine - Qatar