Tumor-driven stromal reprogramming in the pre-metastatic lymph node

Abstract

Background Metastatic dissemination is critically reliant on the formation of a receptive niche, a process which is thought to rely on signals derived from the primary tumor. Lymph nodes are continuously exposed to such signals through the flow of afferent lymph, allowing the potential reprograming of lymphoid tissue stroma in support of metastases or immunosuppression. The objective of this study was therefore to better characterize tumor-driven transcriptomic changes occurring to specific stromal populations within the tumor-draining lymph node. Methods We utilize single cell RNA sequencing of dissociated LN tissue extracted from tumor-bearing and naïve mice to profile the reprograming of tissue stroma within the pre-metastatic lymph node. Results Resulting data provides transcriptomic evidence of tumor-induced imprinting on marginal reticular cells (MRCs) and floor lymphatic endothelial cells (fLECs) populating the subcapsular sinus. These alterations appear to be unique to the tumor-draining LN and are not observed during inflammatory antigenic challenge. Notably, MRCs exhibit characteristics reminiscent of early desmoplastic CAF differentiation, fLECs engage distinct chemoattractant pathways thought to facilitate recruitment of circulating cancer cells, and both stromal populations exhibit signs of metabolic reprograming and immune-modulating potential. Conclusions Cumulatively, these findings build upon existing literature describing pre-metastatic niche formation and offer several promising avenues for future exploration.