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Visible light reprograms MSCs and T cells into tumor-suppressive states via OPN4-mediated epigenetic remodeling

Yin-Zhi Xu1, Zhao-Yuan Xu1, Uma K Aryal2,3

  • 1Weldon School of Biomedical Engineering, Purdue University Indianapolis, Indianapolis, IN, 46202, USA.

Acta Pharmacologica Sinica
|July 6, 2026
PubMed

Insights

Optical pulses can reprogram cells to fight cancer. Blue light kills tumor cells directly, while green and red light convert mesenchymal stem cells (MSCs) into tumor-suppressing cells, offering new therapeutic strategies.

Area of Science:

  • Oncology
  • Cell Biology
  • Biophysics

Background:

  • Cellular metabolism is crucial for tumor resistance.
  • Biophysical stimulations (mechanical, electrical) can reprogram mesenchymal stem cells (MSCs) and T cells towards anti-tumor functions.
  • Investigating optical pulses (OP) as a novel biophysical stimulus for anti-tumor reprogramming.

Purpose of the Study:

  • To determine if optical pulses (OP) can create an anti-tumor microenvironment.
  • To compare OP effects with mechanical and electrical stimulation.
  • To elucidate the mechanisms of OP-induced cellular reprogramming.

Main Methods:

  • Optical stimulation (blue, green, red light) of MSCs and T cells.
  • Comparison with mechanical and electrical stimulation.
  • Assessment of conditioned medium (CM) in breast cancer and osteoclast models.
  • Analysis of OPN4 and Piezo1 pathway involvement.
  • Epigenetic analysis (histone marks, NAD+/NADH ratio).
  • Proteomic profiling of CM.

Main Results:

  • Blue light induced direct tumor cell death.
  • Green and red light converted MSCs into induced tumor-suppressing (iTS) cells via OPN4, independent of Piezo1.
  • OP treatment altered epigenetic marks (reduced H3K9me3) and metabolic state (increased NAD+/NADH ratio).
  • CM from optically stimulated cells contained TFRC and ANXA2, potentially suppressing tumors via CD44 and reducing PD-L1 expression.

Conclusions:

  • Visible light pulses can epigenetically reprogram MSCs and T cells into an anti-tumor state.
  • OPs offer a color-specific approach to modulating the tumor microenvironment.
  • This presents a potential novel therapeutic strategy for breast cancer and bone metastasis.

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