Amazing stuff! Cancer is history (soon)!
"In many tumors, nerves from our peripheral nervous system establish themselves in the cancerous tissue. The new study found that tumors can hijack these nerves to send signals to the brain. This, in turn, triggers activity that blocks immune cells from infiltrating the cancer, which enables cancer growth. ...
The team then sought to understand why this happens. Using animal models of lung adenocarcinoma, they experimented with inhibiting and activating various subpopulations of neurons to see how this impacted cancer growth. They also used single cell sequencing to identify the types of neurons innervating tumors in the lung, as well as imaging techniques to visualize how nerve and cancer cells interacted with one another. Meanwhile, collaborators at the University of Pennsylvania studied the surrounding immune cells and their signaling in the cancer microenvironment. ..."
From the abstract:
"Body–brain communication has emerged as a key regulator of tissue homeostasis. Solid tumours are innervated by different branches of the peripheral nervous system and increased tumour innervation is associated with poor cancer outcomes. However, it remains unclear how the brain senses and responds to tumours in peripheral organs, and how tumour–brain communication influences cancer immunity.
Here we identify a tumour–brain axis that promotes oncogenesis by establishing an immune-suppressive tumour microenvironment.
Combining genetically engineered mouse models with neural tracing, tissue imaging and single-cell transcriptomics, we demonstrate that lung adenocarcinoma induces innervation and functional engagement of vagal sensory neurons, a major interoceptive system connecting visceral organs to the brain.
Mechanistically, Npy2r-expressing vagal sensory nerves transmit signals from lung tumours to brainstem nuclei, driving elevated sympathetic efferent activity in the tumour microenvironment. This, in turn, suppresses anti-tumour immunity via β2 adrenergic signalling in alveolar macrophages.
Disruption of this sensory-to-sympathetic pathway through genetic, pharmacological or chemogenetic approaches significantly inhibited lung tumour growth by enhancing immune responses against cancer.
Collectively, these results reveal a bidirectional tumour–brain communication involving vagal sensory input and sympathetic output that cooperatively regulate anti-cancer immunity; targeting this tumour–brain circuit may provide new treatments for visceral organ cancers."
Fig. 1: LUAD is innervated by VSNs. [vagal sensory neuron]
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