087 Tumor assembly of the spatially organized self-propagating myeloid niche

Cancer immunotherapies have revolutionized treatment, but disappointing results in single-agent regiments reveal the need to understand origin and assembly of tumor immune niche identify further targets highly heterogeneous microenvironment. We previously focused on resistance mechanisms primarily driven by epithelial heterogeneity skin basal cell carcinoma (BCC), identifying discrete subpopulations resistant canonical therapies. Here, we used a combination single-cell imaging-based spatial analysis define extensive specific supportive microenvironmental surrounding BCC epithelia. key spatially organized population TREM2+ cancer-associated myeloid cells (SCAMs), which support proliferation through an oncostatin M mediated signaling pathway. Interestingly, SCAMs are dramatically distinct from found normal homeostatic or during wound healing express unique surface markers that can distinguish them. A feature is their ability actively proliferate within propagate themselves even serial passaging. In turn, find SCAM development tumor, with intratumoral injections demonstrating environment sufficient instruct naive monocyte maturation into functional self-propagating SCAM. Overall, this work suggests targeting conjunction other immunotherapeutics may prove useful strategy.