Sulforaphane impaired immune checkpoint blockade therapy through activating ΔNP63α/PD-L1 axis in gastric cancer

Qi Zhang1, Chenying Yang2, Zhijian Ma3

  • 1Department of Public Health, School of Medicine, Nanjing University of Chinese Medicine, Nanjing, China.

PubMed

Insights

Sulforaphane (SFN) suppresses gastric cancer growth but upregulates PD-L1, potentially hindering anti-PD-L1 therapy. This study reveals SFN

Area of Science:

  • Oncology
  • Cancer Biology
  • Immunotherapy

Background:

  • Sulforaphane (SFN) shows anticancer properties in various cancers, including gastric cancer.
  • The impact of SFN on programmed death-ligand 1 (PD-L1) and its role in gastric cancer immunotherapy remain unclear.

Purpose of the Study:

  • To investigate the effect of SFN on gastric cancer cell growth.
  • To elucidate the mechanism by which SFN regulates PD-L1 expression.
  • To determine the influence of SFN on the efficacy of anti-PD-L1 monoclonal antibody (α-PD-L1 mab) therapy in gastric cancer.

Main Methods:

  • In vitro and in vivo studies of SFN on gastric cancer cells.
  • Analysis of PD-L1 expression regulation by SFN, focusing on ΔNP63α.
  • Assessment of the combined effect of SFN and α-PD-L1 mab on gastric cancer cells.

Main Results:

  • SFN demonstrated suppression of gastric cancer cell proliferation in both experimental settings.
  • SFN was found to increase PD-L1 expression by activating ΔNP63α in gastric cancer cells.
  • The presence of SFN diminished the therapeutic efficacy of α-PD-L1 mab against gastric cancer cells.

Conclusions:

  • SFN exhibits a dual role in gastric cancer, inhibiting tumor growth while potentially compromising immunotherapy.
  • A novel mechanism of PD-L1 regulation by SFN via ΔNP63α activation in gastric cancer is identified.
  • Findings suggest careful consideration of SFN use in combination with PD-L1 blockade therapy for gastric cancer patients.

Related Concept Videos

Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.3K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
7.6K