乳腺癌 z-bio 2025-08-09 3571

　　For a long time, clinical observations have shown that interacting with others may slow down the progression of cancer and help patients recover better. This is especially true for breast cancer patients, who, after engaging more in social activities, not only experience less anxiety but also have a longer survival period. Is there a connection between these two?

　　Existing research has shown that the anterior cingulate cortex (ACC) is involved in the regulation of emotions and social behavior, while the basolateral amygdala (BLA) is associated with anxiety and social interaction, and the two have neural connections. However, it is still unclear how social interaction affects cancer progression through these brain regions and related circuits.

　　On August 1st, a study conducted by the Military Medical University of the People's Liberation Army (Third Military Medical University) and its affiliated Southwest Hospital made headlines on the official website of Cell Press, precisely addressing this issue.

　　Wu Guangyan, Xiong Ying, Dai Limeng, and Zhang Yi jointly published a research paper titled "Social interaction in mice suppresses breast cancer progression via a corticoamygdala neural circuit" in Neuron.

　　This study is the first to clearly demonstrate that social interaction inhibits the progression of breast cancer in mice by activating the neural circuit of "glutamatergic neurons in the anterior cingulate cortex → glutamatergic neurons in the basolateral amygdala", and elucidates the complete mechanism through which it regulates sympathetic nerve activity and the tumor immune microenvironment. It also confirms that artificially regulating this circuit can mimic the anti-tumor effect of social interaction, providing key evidence for the application of social support in cancer treatment and the development of neural regulatory therapies.

　　Research Highlights

　　▶  Social interaction inhibits breast cancer progression by activating neural circuits

　　▶  The anterior cingulate cortex glutamatergic neurons (ACCGlu) are key to social interaction and play an anti-tumor role

　　▶  The anti-tumor benefits of ACCGlu → basal lateral amygdala glutamatergic neuron (BLAGlu) circuit mediated social interaction

　　▶  Artificial reactivation of social interaction related circuits can enhance anti-tumor immunity

　　Research content

　　The research team took 4T1 breast cancer model mice and MMTV PyMT spontaneous breast cancer model mice as objects, set up social interaction groups with different duration (1 hour, 2 hours or 24 hours a day with healthy peers) and single feeding groups (0 hour social interaction), and carried out research in combination with behavioral evaluation, neural regulation technology and molecular immune analysis.

　　Behavioral experiments have shown that regardless of the duration of social interaction, anxiety like behavior in tumor mice can be significantly reduced (validated through light dark box, open field, and elevated cross maze experiments), while inhibiting tumor growth - reducing tumor volume, weight, and fluorescence intensity, decreasing the proportion of proliferating cells (Ki67 ⁺) within the tumor, and increasing the proportion of apoptotic cells (TUNEL ⁺), and this effect is independent of the "rich environment" (non living object stimulation).

　　In terms of neural mechanisms, it was found through extracellular recording and fiber optic photometry that social interaction activates glutamatergic neurons (ACC ᵍˡᵘ) in the ACC, and their firing rate further increases during social contact; And there is a direct projection from ACC ᵍˡᵘ to the glutamatergic neurons of BLA (BLA ᵍˡᵘ) (ACC ᵍˡᵘ → BLA ᵍˡᵘ circuit). Chemical genetic experiments have confirmed that inhibiting the ACC ᵍˡᵘ or ACC ᵍˡᵘ → BLA ᵍˡᵘ circuit can eliminate the anti anxiety and anti-tumor effects of social interaction; Artificially activating this circuit can simulate the effect of social interaction and reduce the level of norepinephrine (NE, a sympathetic nervous system activity indicator) in tumors.

　　Further research has found that this circuit regulates the microcircuits within the amygdala (BLA ᵍˡᵘ → CeL ᵍᵃᵇᵃ → CeM ᶜʳʰ), inhibits the activity of CRH neurons in the central medial amygdala (CeM ᶜʳʰ), and thereby reduces sympathetic nerve activity within the tumor. Molecular immune analysis shows that social interaction or artificial activation of the above circuits can improve the tumor immune microenvironment: increase the proportion of CD4 ⁺ and CD8 ⁺ T cells, reduce myeloid suppressor cells (MDSCs) and regulatory T cells (Tregs), and enrich T cell differentiation and immune checkpoint pathway related genes.

　　Key issues

　　1. What is the core neural circuit that social interaction inhibits the progress of breast cancer? What is its functional pathway?

　　Answer: The core circuit is composed of glutamatergic neurons in the anterior cingulate cortex (ACC ᵍˡᵘ) → glutamatergic neurons in the basolateral amygdala (BLA ᵍˡᵘ).

　　Action pathway: Social interaction activates ACC ᵍˡᵘ, whose excitatory projection enhances BLA ᵍˡᵘ activity, which in turn activates GABAergic neurons (CeL ᵍᵃᵇᵃ) in the central lateral amygdala. Through feedforward inhibition, the activity of CRH neurons (CeM ᶜʳʰ) in the central medial amygdala is reduced, ultimately suppressing sympathetic nerve activity within the tumor (reducing NE release).

　　How to verify that the ACC ᵍˡᵘ → BLA ᵍˡᵘ circuit is the key to social interaction exerting anti-tumor effects?

　　Answer: Through two experimental verifications: ① Necessity: After chemical genetic inhibition of the ACC ᵍˡᵘ or ACC ᵍˡᵘ → BLA ᵍˡᵘ circuit, the anti anxiety (such as reduced EPM open arm time) and anti-tumor (such as increased tumor weight) effects of social interaction disappear; ② Adequacy: Manually activating this circuit (without social interaction) can simulate the effects of social interaction, significantly reducing tumor growth rate (such as a volume reduction of about 45% in the 4T1 model within 24 days) and NE levels (a reduction of about 40%).

　　To sum up, this study reveals that social interaction can inhibit sympathetic nerve activity in tumor and enhance anti-tumor immunity by activating ACC → BLA neural circuit, thus slowing down the progress of breast cancer in mice. This discovery clarifies the neural mechanism by which social interaction exerts anti-tumor effects, providing a scientific basis for incorporating social support into clinical cancer treatment and laying the foundation for the development of novel cancer therapies targeting neural circuits.