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Gene expression is surprisingly coordinated across the tumor microenvironment

Mikaël Pittet, Ludwig Cancer Research Lausanne
Mikaël Pittet

To examine how much the tumor microenvironment (TME) varies between tumors, researchers led by Ludwig Lausanne’s Mikaël Pittet conducted an unbiased analysis of 52 primary and metastatic tumors from 51 patients with head and neck cancers, examining how global gene expression captured in individual cells but statistically analyzed across tumors as a whole corresponds to patient outcomes. They reported in an August paper in Science that patients with higher expression of the gene CXCL9 in their tumor-associated macrophages (TAMs) had far better clinical outcomes than those with higher expression of a gene named SPP1 by the immune cells. TAMs expressing the former gene, they showed, are invariably poised to attack cancer cells, while those expressing SPP1 are in a state supportive of tumor growth. Most intriguing, however, was their discovery that when the ratio of CXCL9 to SPP1 is high in TAMs, gene expression programs in other TME cells indicate a similarly anti-tumor slant; a low ratio of the two (termed CS), on the other hand, invariably accompanies pro-tumor gene expression signatures across other cell types in the TME. With further validation in prospective studies, Mikaël and his colleagues noted, the CS ratio could prove to be an easily measured molecular marker of patient prognosis for the management of therapy.

CXCL9:SPP1 macrophage polarity identifies a network of cellular programs that control human cancers
Science, 2023 August 3

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