Investigating the contribution of early and late disseminated tumor cells in lung metastasis progression

Recent pioneering work in the field has not only described the presence of early neoplasm-derived cancer cells in the metastatic niche but has elucidated several underlying mechanisms responsible for their seeding. Yet, it remains unclear how early cancer cells interact with their new cellular environment once disseminated. In the present work, we aimed to address the knowledge gap related to how the immune microenvironment responds to and influences the fate of early compared to later arriving disseminated tumor cell (DTC) seeds. To distinguish early vs. late seeding cancer cells, we first engineered barcoded cancer cell lines and then conducted multiple, staggered injections in a triple negative breast cancer (TNBC) lung metastasis context. Our preliminary data showed that early timepoint injected cancer cells preferentially proliferate despite not harboring genetic and transcriptomic advantages compared to later arriving cancer cells. Furthermore, single cell RNA-seq analysis of barcoded cancer cells extracted from lung metastases and immune cells revealed an anti-inflammatory tumor associated macrophage (TAM) cluster expressing high triggering receptor expressed on macrophages 2 (Trem2) program genes and complement component q (C1q).