# Lymphatic Endothelial Cells and Organ-Associated Lymphangiogenesis in Tumor Microenvironment

## TL;DR

This paper explores how lymphatic endothelial cells and lymphatic vessels influence cancer progression and metastasis, highlighting their dual roles and potential as therapeutic targets.

## Contribution

The paper provides new insights into the heterogeneity of LECs and their role in organ-specific lymphangiogenesis within the tumor microenvironment.

## Key findings

- Lymphatic endothelial cells (LECs) exhibit heterogeneity and plasticity, influencing lymphatic function in different organs.
- Lymphatic vessels have a dual role in promoting and inhibiting cancer progression and metastasis.
- Organ-specific lymphangiogenesis is regulated by signaling pathways in the tumor microenvironment.

## Abstract

What are the main findings?
LECs have heterogeneous and plastic features.Lymphatic vessels have a dual role in cancer progression and metastasis.Organ-associated lymphangiogenesis is regulated by various signaling pathways in TME.

LECs have heterogeneous and plastic features.

Lymphatic vessels have a dual role in cancer progression and metastasis.

Organ-associated lymphangiogenesis is regulated by various signaling pathways in TME.

What are the implications of the main findings?
Functional diversity of LECs will contribute to elucidating the pathogenic mechanism of lymphatic-related diseases.Lymphatic modulation is focused on inhibiting pro-metastatic functions and enhancing protective anti-tumor immunity.Intervention of organ-specific lymphangiogenesis may be promising for molecular target and gene therapy.

Functional diversity of LECs will contribute to elucidating the pathogenic mechanism of lymphatic-related diseases.

Lymphatic modulation is focused on inhibiting pro-metastatic functions and enhancing protective anti-tumor immunity.

Intervention of organ-specific lymphangiogenesis may be promising for molecular target and gene therapy.

Lymphatic vessels are a kind of heterogeneous and versatile component of the lymphatic system, with a unique ability to respond to environmental changes in different organs. The heterogeneity and plasticity of lymphatic endothelial cells (LECs) and defective lymphatic architecture are critical for organ-specific lymphatic function. Moreover, lymphatic vessels have a dual effect on tumor microenvironment (TME), and lymphangiogenesis, an active and dynamic player, is a hallmark of cancer progression and treatment resistance. Dysregulation of lymphatic vessels and uncontrolled lymphangiogenesis contribute to the pathogenesis of many diseases, including cancer. Increasing evidence has indicated that lymphangiogenesis provides a critical target for inhibiting lymphatic metastasis, in which immune checkpoint inhibitors, either alone or combined with chemotherapy, may have a therapeutic value. This article reviews the current status of tumor-associated lymphangiogenesis and lymphatic remodeling, as well as the crosstalk among LECs, immune cells and cancer cells, which will help to further understand the role of lymphangiogenesis in cancer progression, metastasis, and therapy.