Macrophages and lymphatic vessels

The term Macrophages and lymphatic vessels refers to a complex cellular and physiological interaction rather than a single molecular target. Macrophages, particularly those with an M2-like or pro-angiogenic phenotype, are critical regulators of lymphangiogenesis—the formation of new lymphatic vessels—by secreting key growth factors such as VEGF-C and VEGF-D (Ran and Montgomery, 2012, PMID: 22439053). These factors bind to VEGFR3 on lymphatic endothelial cells, stimulating vessel sprouting and expansion. In oncology, tumor-associated macrophages (TAMs) exploit this mechanism to increase peritumoral lymphatic density, which facilitates the migration of cancer cells to regional lymph nodes and promotes systemic metastasis (Kataru et al., 2019, PMID: 31160537). Beyond cancer, this interaction is essential for resolving chronic inflammation and maintaining fluid balance, as macrophages help remodel lymphatic networks to clear edema and transport immune cells. Because this is a multi-component system, drug development focuses on specific molecular nodes within the axis, such as VEGFR3 or CSF1R, to either inhibit pathological vessel growth in tumors or potentially stimulate lymphatic repair in conditions like lymphedema.

Other names

Macrophage-lymphatic axisLymphangiogenic macrophagesTAM-lymphatic interactionMyeloid-lymphatic signaling

Therapeutic modulation of this axis typically involves the inhibition of pro-lymphangiogenic growth factors (e.g., VEGF-C) or their cognate receptors (e.g., VEGFR3) to prevent the expansion of lymphatic networks, or the targeting of macrophage recruitment and polarization (e.g., via CSF1R or CCL2 inhibition) to reduce the cellular source of lymphangiogenic stimuli.