Deciphering tumor microenvironment: CXCL9 and SPP1 as crucial determinants of tumor-associated macrophage polarity and prognostic indicators

Abstract The tumor microenvironment (TME) is an intricate system comprised of tumor cells and the surrounding cellular and non-cellular components, exerting a pivotal influence on the initiation and progression of tumors. Exhibiting dynamic and diverse compositions as well as functional states across various tumors and patients, a profound comprehension of its specific internal interactions is indispensable for formulating efficacious anti-cancer treatment strategies. Extensive interactions among various immune cell types within the TME are well-documented, with their phenotypes and abundances closely linked to clinical prognoses. TME research is progressing towards greater complexity and precision, yet, to date, no representative TME biomarkers suitable for clinical applications have been definitively identified and validated. In a recent study, the collaborative actions of CXCL9 and SPP1 (CXCL9:SPP1) were found to collectively dictate the polarity of tumor-associated macrophages (TAMs) within the TME, exerting profound effects on tumor progression and treatment responses. The mutually exclusive expression of CXCL9:SPP1 in the TME not only governs TAM polarity but also exhibits strong correlations with immune cell profiles, antitumor factors, and patient outcomes, significantly influencing prognosis. This article consolidates the significance and prospects of CXCL9:SPP1 as a novel indicator for tumor development and prognosis, while also proposing future research directions and addressing potential challenges in this promising field.