Scientists Uncover Startling—and Exploitable—Coordination of Gene Expression in Tumors

A Ludwig Cancer Research study has identified a pair of genes whose expression by a type of immune cell within tumors is predictive of outcomes for cancer patients and is linked to a vast network of gene expression programs, engaged by multiple cell types in the tumor microenvironment (TME), that control human cancers. Researchers led by Ludwig Lausanne’s Mikaël Pittet, PhD, report in the August 3, 2023 issue of Science that patients with higher expression of the gene CXCL9 in their tumor-associated macrophages had far better clinical outcomes than those with higher expression of a gene named SPP1 by the immune cells. Macrophages expressing the former gene, they show, are invariably poised to attack cancer cells, while those expressing SPP1 are in a state supportive of tumor growth. Most intriguing, however, is the discovery that when the ratio of CXCL9 to SPP1 is high, gene expression programs in other TME cells indicate a similarly anti-tumor slant; a low CS ratio, on the other hand, invariably accompanies pro-tumor gene expression signatures across the TME. The Science article is titled “CXCL9:SPP1 Macrophage Polarity Identifies a Network of Cellular Programs That Control Human Cancers.”