Cell reports. MedicineSep 1, 2026

Using gene activation to turn brain cancer cells into immune-like cells that trigger body-wide tumor defense

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗

Updated Sep 2, 2026

Abstract

Transcription factors Zfp366/Znf366, Pu.1, Irf8, and Batf3 (ZPIB) can convert glioblastoma (GBM) cells into dendritic cell-like cells.

ZPIB-mediated reprogramming leads to significant changes in gene expression and cellular structure in GBM cells.
Single-cell RNA sequencing shows effective reprogramming of GBM cells to dendritic cells in living organisms.
Reprogrammed tumor cells alter the surrounding microenvironment and trigger strong immune responses against tumors in mouse models.
The immune response generated by ZPIB-modified dendritic cells works in combination with immune checkpoint inhibitors.
ZPIB-derived dendritic cells can be generated from GBM patients, indicating potential for clinical application.

Simplified

Although immunotherapy has transformed the treatment landscape for many types of cancer, its therapeutic efficacy in glioblastoma (GBM) is limited by insufficient antigen presentation and the immunogenic cell exclusion in the tumor microenvironment. Here, we develop a candidate-based CRISPR activation (CRISPRa) functional screen to identify regulators of conventional dendritic cell (cDC)-fate specification. We determine that the transcription factors Zfp366/Znf366, Pu.1, Irf8, and Batf3 (ZPIB) are sufficient to convert GBM cells into cDC-like cells. ZPIB-mediated reprogramming results in global transcriptional and epigenetic remodeling in glioma cells. Single-cell RNA sequencing (scRNA-seq) profiling also reveals efficient and dynamic reprogramming of GBM cells to cDCs in vivo. Moreover, reprogrammed tumor cells remodel the microenvironment and elicit systemic tumor-eradicating and durable antitumor immunity in multiple mouse GBM models. Antitumor immunity elicited by ZPIB-DCs is synergistic with immune checkpoint inhibitors. Finally, we evaluate the clinical applicability of this approach by generating ZPIB-DCs from GBM patients within a humanized model. Our study represents a cellular reprogramming therapeutic strategy with broad implications for clinical immunotherapy.

Full Text

Full text is available at the source.

View Full Text ↗

Featured in

CRISPR Gene EditingIssue #53

A single AAV injection corrected progeria mutations in mouse bone — timing was everything

↗

Using gene activation to turn brain cancer cells into immune-like cells that trigger body-wide tumor defense

Abstract

Full Text

Featured in

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the crispr gene editing brief