Bill and Wirapati et al. asked if common TME cellular processes control complex and variable patient outcomes. Single-cell analysis of 52 head and neck squamous cell carcinomas revealed tumor-associated macrophages (TAMs) were major contributors to patient outcomes, and TAM polarity, defined by the ratio of CXCL9 and SPP1 (CS) expression, but not by M1 or M2 markers, had strong prognostic association. CS TAM polarity was increased by IFNγ and decreased by hypoxia. Patients with CXCL9hi TAMs had better outcomes than patients with SPP1hi TAMs. CS TAM polarity identified co-regulated networks of cellular programs in the TMEs of various human cancers.
Contributed by Katherine Turner
ABSTRACT: Tumor microenvironments (TMEs) influence cancer progression but are complex and often differ between patients. Considering that microenvironment variations may reveal rules governing intratumoral cellular programs and disease outcome, we focused on tumor-to-tumor variation to examine 52 head and neck squamous cell carcinomas. We found that macrophage polarity-defined by CXCL9 and SPP1 (CS) expression but not by conventional M1 and M2 markers-had a noticeably strong prognostic association. CS macrophage polarity also identified a highly coordinated network of either pro- or antitumor variables, which involved each tumor-associated cell type and was spatially organized. We extended these findings to other cancer indications. Overall, these results suggest that, despite their complexity, TMEs coordinate coherent responses that control human cancers and for which CS macrophage polarity is a relevant yet simple variable.