Intrinsic RB activation induces tumoral and stromal anti-tumor responses that limit triple-negative breast cancer

Area of Science:

• Oncology
• Cancer Biology
• Immunology

Background:

• The RB tumor suppressor is crucial for cell cycle regulation.
• RB is frequently inactivated in triple-negative breast cancer (TNBC).
• RB activation shows potential for anti-cancer effects in the tumor and its microenvironment (TME).

Purpose of the Study:

• To investigate the intrinsic sufficiency of RB activation in suppressing TNBC.
• To assess RB's effects on TNBC cell proliferation and the TME.

Main Methods:

• Utilized a constitutively active RB protein (RBΔCDK) in TNBC cell lines.
• Performed transcriptomic analysis to identify gene expression changes.
• Evaluated tumor growth and metastasis in xenograft and syngeneic mouse models.

Main Results:

• RBΔCDK expression uniformly inhibited TNBC cell proliferation.
• Transcriptomic analysis showed suppressed cell cycle genes and induced interferon response genes.
• Tumor growth and metastasis were significantly reduced in RBΔCDK-expressing models.
• RB activation altered the TME, with CD8+ T cells mediating tumor suppression.

Conclusions:

• Active RB is intrinsically sufficient to suppress TNBC progression.
• RB suppresses TNBC through both cancer cell-autonomous and non-autonomous mechanisms.
• RB activation holds therapeutic potential for TNBC by modulating the immune response within the TME.