Decoding the spatial dynamics of tumor and immune cell interactions in solid cancers.

The spatial landscape of the tumor immune microenvironment (TIME) is under significant investigation as a driver of immunotherapy resistance in solid tumors. Most work centers on constituent immune cells within intra-tumoral niches, overlooking tumor cell phenotypes. Yet cancer cells shape their milieu by multiple modalities, including secreting and depleting metabolites. Here, we argue that integrating cancer cell phenotypic heterogeneity into spatial analyses is essential to reveal the mechanisms that generate TIME diversity and to better address resistance to immunotherapy.