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A searching analysis of TANs yields clues to improving brain tumor therapy

Johanna Joyce, Ludwig Cancer Research Lausanne
Johanna Joyce

A team led by Ludwig Lausanne’s Johanna Joyce and Roeltje Maas, a former MD-PhD student in her laboratory, detailed in a September paper in Cell the findings of an integrated, multifactorial analysis of neutrophils in more than 190 brain tumor samples from patients and experiments in mouse models of brain cancer. They reported multiple ways in which neutrophil phenotypes—or physical traits and functional states—differ from that of their counterparts in the circulation and in healthy brain tissues. Johanna, Roeltje and colleagues found that tumor-associated neutrophils (TANs) are more abundant in brain metastases from the lungs, breast and skin than in primary gliomas and tend to cluster around malformed blood vessels in tumors. TANs switch off gene expression programs that induce cell death while turning on genes that support cell survival—thus lengthening their lifespans. They churn out factors that stimulate the formation of blood vessels, become functionally suppressed—halting production of the reactive oxygen species they use to destroy cellular targets—and appear to actively suppress the types of T cells that target tumors. The researchers also identified specific cellular interactions and inflammatory factors in the microenvironment—TNF-α and ceruloplasmin—that are key to turning neutrophils into abettors of malignancy. The findings suggest new approaches to the treatment of both gliomas and brain metastases.

The local microenvironment drives activation of neutrophils in human brain tumors
Cell, 2023 September 27

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