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CRISPR-based metabolic screening identifies PLCE1 as a pivotal regulator of oncolytic viral antitumor immunity via

Yanqin Xu1, Yalu Wu1, Hao Zheng2

  • 1College of Life Science, Nankai University, Tianjin, China; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China.

Biochemical and Biophysical Research Communications
|February 27, 2026
PubMed

Insights

This study identifies phospholipase C epsilon 1 (PLCE1) as a target to overcome tumor resistance to oncolytic viruses (OV). Inhibiting PLCE1 enhances OV therapy, improving immune response and reducing tumor growth.

Area of Science:

  • Oncology
  • Immunotherapy
  • Molecular Biology

Background:

  • Oncolytic viruses (OV) are promising cancer immunotherapeutics but face intrinsic tumor resistance.
  • This resistance limits the efficacy of OV monotherapy.

Purpose of the Study:

  • To identify novel targets to enhance OV efficacy.
  • To investigate the role of phospholipase C epsilon 1 (PLCE1) in OV resistance.

Main Methods:

  • CRISPR-Cas9 metabolic gene screening in MC38 colorectal cancer models.
  • In vitro assessment of OV infection and cell death with PLCE1 inhibitor U-73122.
  • In vivo efficacy studies combining U-73122 and OV in tumor models.
  • Analysis of tumor immune microenvironment modulation.

Main Results:

  • PLCE1 was identified as a key negative regulator of OV antitumor effects.
  • PLCE1 inhibition by U-73122 enhanced OV infection and immunogenic cell death in vitro.
  • Combination therapy synergistically reduced tumor volume and prolonged survival in vivo.
  • The therapy remodeled the tumor immune microenvironment, increasing CD8+ T cells and decreasing regulatory T cells.

Conclusions:

  • PLCE1 is a novel therapeutic target for overcoming resistance to oncolytic virotherapy.
  • Targeting PLCE1 can enhance OV efficacy and promote a potent antitumor immune response.
Keywords:
CRISPR-Cas9Cancer immunotherapyColorectal cancerOncolytic virusesPLCE1Tumor immune microenvironment

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