What does this research mean for the field?

Weight loss via dietary changes or GLP-1R agonism decreases C1q expression and suppresses obesity-driven breast tumor growth by reversing an immunosuppressive macrophage-driven microenvironment. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

The research aims to explore how obesity influences the immune environment associated with breast cancer.

April 5, 2026

Abstract 6572: Obesity shapes a reversible immune microenvironment that fosters breast cancer growth

Key Result

Weight loss via dietary changes or GLP-1R agonism decreased C1q expression and suppressed obesity-driven breast tumor growth in mouse models.

Key Points

The research aims to explore how obesity influences the immune environment associated with breast cancer.
Used single-cell RNA sequencing in mouse models of obesity and breast cancer
Identified roles of C1q+ macrophages in mammary tumors and adipose tissue
Examined effects of C1q, TNF-α, and PGE2 synthesis blockade on tumor growth
Assessed impact of weight loss through diet and GLP-1R agonism on tumor dynamics
C1q+ macrophages promote tumor-associated immunosuppression and tumor growth in obesity
Blockade of C1q and PGE2 synthesis resulted in reduced tumor growth
Weight loss strategies decreased C1q expression and suppressed obesity-driven tumor growth
Highlights the potential of targeting the immune microenvironment to improve breast cancer outcomes

Structured PICO

Population

Mouse obesity and breast cancer models

Intervention

Blockade of C1q, TNF-α, and PGE2 synthesis; weight loss via dietary changes or GLP-1R agonism

Outcome

Tumor growth and C1q expressionsurrogate

In mouse models, obesity-driven breast cancer growth is mediated by C1q+ macrophages and can be reversed by weight loss or GLP-1R agonism.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

Abstract Obesity is linked to breast cancer risk and severity, yet the underlying mechanisms remain unclear. Using single-cell RNA sequencing, we identified a role for C1q+ macrophages in mammary tumors and adipose tissues in mouse obesity and breast cancer models. Macrophage-derived C1q promotes the clearance of obesity-associated apoptotic adipocytes, enhancing lipid metabolism and leading to an immunosuppressive tumor microenvironment via the production of prostaglandin E2 (PGE2). Moreover, the tumor-associated macrophages (TAMs) engage tumor cells in a feedforward loop by inducing the production of monocyte-recruiting cytokines further suppressing the anti-tumor immune response. Blockade of C1q, TNF-α, and PGE2 synthesis reduced tumor growth in obese mice. Importantly, weight loss via dietary changes or glucagon-like peptide-1 receptor (GLP-1R) agonism decreased C1q expression and suppressed obesity-driven tumor growth. Interference with the immunosuppressive environment and the feedforward loop may be viable strategies for improving the outcomes of breast cancer patients with obesity. Citation Format: Tao Zhang, Shimeng Liu, Yi Zhang, Alva Yijia Jiang, Zachary Sandusky, Na Zhang, Tara Akhshi, Nicole Traphagen, Jack Yueyang Wang, Lucas Tian, Esme Wheeler, Yingtian Xie, Rong Li, Buraq Ahmed, Genevra Kuziel, Capucine Heraud, Mohammed Mutaher, Henry Long, Kornelia Polyak, Myles A. Brown. Obesity shapes a reversible immune microenvironment that fosters breast cancer growth abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6572.

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