Work

ITGB1 Regulates Triple‐Negative Breast Cancer Development by Modulating the Tumor Microenvironment

Year: 2026

Type: article

Abstract: Tumorigenesis and metastasis are frequently attributed to the intricate interplay between cancer cells and the tumor microenvironment (TME). Comprehending the mechanisms and key regulators of cancer-immune crosstalk in the TME is imperative for developing efficacious immunotherapy. Through a series of in vivo CRISPR screens, we identified tumor-intrinsic ITGB1 as a critical regulator of triple-negative breast cancer (TNBC) development and deciphered its underlying mechanisms. Tumoral ITGB1 facilitated the establishment of pro-tumorigenic TME by orchestrating tumor-associated myeloid populations. Suppressing ITGB1 favored the enrichment of anti-tumorigenic myeloid cells and enhanced infiltration of CD4 and CD8 T cells, culminating in superior antitumor effects. CRISPR scanning pinpointed a previously unrecognized functional domain essential for ITGB1's pro-tumorigenic activity. This domain is distinct from all known ligand-binding sites in ITGB1. An antibody capable of sterically blocking this domain significantly impaired TNBC progression. These findings position tumoral ITGB1 as a promising therapeutic target for reprogramming the TME from a pro- to an anti-tumorigenic state, thereby effectively inhibiting TNBC development. Our study uncovers a novel mechanism of TNBC development and provides a unique therapeutic strategy for targeting ITGB1 in TNBC treatment.

Source: Advanced Science

DOI: 10.1002/advs.202513672