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

TL;DR

This study explores how tumors change nearby lymph node cells to create a welcoming environment for cancer spread.

Contribution

The study identifies specific stromal cell changes in pre-metastatic lymph nodes driven by tumors.

Findings

Tumor-induced changes occur in marginal reticular cells and floor lymphatic endothelial cells.

These changes include metabolic reprogramming and immune-modulating potential.

The alterations are unique to tumor-draining lymph nodes and not seen in inflammation.

Abstract

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.

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.

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.

Cumulatively, these findings build upon existing literature describing pre-metastatic niche formation and offer several promising avenues for future exploration.

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