Comparison of Lean, Obese, and Weight-Loss Models Reveals TREM2 Deficiency Attenuates Breast Cancer Growth Uniquely in Lean Mice and Alters Clonal T-cell Populations

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Obesity is an established risk factor for breast cancer development and poor prognosis. The adipose environment surrounding breast tumors, which is inflamed in obesity, has been implicated in tumor progression, and triggering receptor expressed on myeloid cells 2 (TREM2), a transmembrane receptor expressed on macrophages in adipose tissue and tumors, is an emerging therapeutic target for cancer. A better understanding of the mechanisms for the obesity-breast cancer association and the potential benefits of weight loss could help inform treatment strategies. In this study, we utilized lean, obese, and weight-loss mouse models to examine the impact of TREM2 deficiency on postmenopausal breast cancer depending on weight history conditions. Trem2 deficiency constrained tumor growth in lean, but not in obese or weight-loss, mice. Single-cell RNA sequencing, in conjunction with variable-diversity-joining sequencing, of tumor and tumor-adjacent mammary adipose tissue immune cells revealed differences in the immune landscapes across the different models. Tumors of lean TREM2-deficient mice exhibited a shift in clonal CD8+ T cells from an exhausted to an effector memory state, accompanied by increased clonality of CD4+ Th1 cells, that was not observed in any other diet-genotype group. Notably, identical T-cell clonotypes were identified in the tumor and tumor-adjacent mammary adipose ti

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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