giovedì, Novembre 21, 2024

Infiammazione cronica silente: la causa sottostante all’anemia cronica dell’anziano

L'invecchiamento è un processo inevitabile che è influenzato dalla...

Brain metastazing is not round-trip: and Interferon shows 1 type of a temper in the process

Several types of cancer are known for metastasizing to the brain, including breast, lung, carcinoma and melanoma. One reason conventional treatments do not work on these cancers after they reach the brain is because the brain is such a different environment from the rest of the body, with unique brain cells (neuron and glia cells) providing different support to the metastatic cancer cells. When cancer that starts in the body metastasizes to the brain, it is almost always lethal, in part because so few treatment options exist. Now a new study by Wistar scientists led by assistant professor Qing Chen, MD, PhD, at the Ellen and Ronald Caplan Cancer Center, shows that a type of brain cell called astrocytes plays an important role in promoting brain metastasis by recruiting a specific subpopulation of immune cells. The finding could be a first step toward identifying potential targets for therapies to fight cancers that metastasize to the brain.

This would fill a significant unmet need, because treatment options for brain metastasis have lagged behind, even as advances in other cancer therapies have made enormous strides, making those cancers much more treatable. For the study, researchers wanted to better understand the cancer-brain interactions that trigger metastasis when cancer cells enter the brain. They focused on astrocytes, a type of star-shaped cell that helps form connections between neurons. Using brain metastasis mouse models, researchers showed that when the astrocytes were exposed to cancer cells, they began to activate type I interferon pathways. Type I interferon have been shown to have to anti-tumor effects. However, more and more evidence suggest controversial effects of type I IFN signaling in chronic inflammation and cancer. This is the first time the type I interferon response had been implicated to promote brain metastasis.

They found that the interferon response was being activated at a low level but for a prolonged period of time. This could explain why a process that is normally associated with helping the immune system was actually causing harm by supporting tumor growth. Previous studies have found that low-level, chronic interferon response can cause negative health outcomes, she noted. When they took a closer look, researchers found that the interferon signaling was activating production of the CCL2 chemokine, attracted harmful immune cells called monocytic myeloid cells that, in turn, promote tumor growth. Of note, CCL2 can be produced by many other resident brain stromal cells including neurons, microglia, oligodendrocytes and even endothelial cells of blood vessels. In the brain metastatic lesions, infiltrated immune cells, as well as cancer cells, can be additional cellular sources of CCL2.

In fact, a previous report has shown that breast cancer cells increase CCL2 production in response to the exosomes secreted from the surrounding astrocytes. Researchers then studied mice that were genetically altered to abolish the type I interferon activation in astrocyte cells. They found that mice that were missing this pathway had fewer brain metastases. That shows the type I interferon response in astrocyte cells actually promotes metastasis. Similar result were also found with both melanoma and breast cancer cells, showing that the process occur across different cancer types. Chen’s team is now applying for a federal grant from the National Cancer Institute for a follow up study, to better understand the mechanism and timing of how astrocytes and the interferon response promote brain metastasis. The goal is to identify the best therapeutic window for treating and stopping this process.

  • Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.

Scientific references

Ma W et al. Nat Commun. 2023 May 6; 14(1):2632.

Hajal C, Shin Y et al. Sci Adv. 2021; 7(26):eabg8139.

Amin S et al. JAMA Netw. Open. 2020; 3:e2015444.

Musella M et al. Oncoimmunology 2017; 6:e1314424.

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Dott. Gianfrancesco Cormaci
Dott. Gianfrancesco Cormaci
Laurea in Medicina e Chirurgia nel 1998; specialista in Biochimica Clinica dal 2002; dottorato in Neurobiologia nel 2006; Ex-ricercatore, ha trascorso 5 anni negli USA (2004-2008) alle dipendenze dell' NIH/NIDA e poi della Johns Hopkins University. Guardia medica presso la casa di Cura Sant'Agata a Catania. Medico penitenziario presso CC.SR. Cavadonna (SR) Si occupa di Medicina Preventiva personalizzata e intolleranze alimentari. Detentore di un brevetto per la fabbricazione di sfarinati gluten-free a partire da regolare farina di grano. Responsabile della sezione R&D della CoFood s.r.l. per la ricerca e sviluppo di nuovi prodotti alimentari, inclusi quelli a fini medici speciali.

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