Immune homeostasis is essential for maintaining immune balance and host defense, while its disruption 9 underlies a broad spectrum of chronic inflammatory diseases and cancers (McInnes and Gravallese, 10 2021). Increasing evidence indicates that cellular and molecular immune heterogeneity within 11 inflammatory and tumor microenvironments critically shapes disease progression and therapeutic 12 response (Hou et al., 2021). Although advances in single-cell and spatial multi-omics technologies 13 have revealed diverse immune cell states and dynamic remodeling of the immune landscape, clinical 14 translation remains limited (Guo et al., 2024). Heterogeneous responses to immune checkpoint 15 blockade (ICB) and targeted therapies, as observed in immunologically "cold" tumors such as 16 pancreatic cancer or in therapy-resistant inflammatory conditions, underscore the need for a deeper 17 understanding of immune heterogeneity (
Zhang et al. (Mon,) studied this question.