Exploiting lymphatic vessels for immunomodulation: Rationale, opportunities, and challenges

Abstract

Lymphatic vessels are the primary route of communication from peripheral tissues to the immune system; as such, they represent an important component of local immunity. In addition to their transport functions, new immunomodulatory roles for lymphatic vessels and lymphatic endothelial cells have come to light in recent years, demonstrating that lymphatic vessels help shape immune responses in a variety of ways: promoting tolerance to self-antigens, archiving antigen for later presentation, dampening effector immune responses, and resolving inflammation, among others. In addition to these new biological insights, the growing field of immunoengineering has begun to explore therapeutic approaches to utilize or exploit the lymphatic system for immunotherapy.

Biomaterials as Tools to Decode Immunity

“…Another important area is how vasculature and lymphatic vessels work with immune cells to support communication and immune signaling. Lymphatic and blood vessels provide a means for the body to transport immune cells, fluids, and signaling molecules across great distances . These lymphatic vessels contain lymphatic endothelial cells (LECs) that regulate immune cell functions by secreting cytokines, expressing ligands that activate immune cells, and displaying molecules that control cellular migration .…”

“…Lymphatic and blood vessels provide a means for the body to transport immune cells, fluids, and signaling molecules across great distances. [118,119] These lymphatic vessels contain lymphatic endothelial cells (LECs) that regulate immune cell functions by secreting cytokines, expressing ligands that activate immune cells, and displaying molecules that control cellular migration. [120] These interactions allow immune cells to communicate with the ECM and vice versa.…”

Deconstructing Immune Microenvironments of Lymphoid Tissues for Reverse Engineering

“…As lymphatic vessels are conduits for immune cells toward lymphoid tissues, LECs do come into direct contact with immune cells and have shown to have some immunomodulatory roles. LECs, too, have been reported to suppress, through contract impairment of DC maturation via adhesion molecules (ICAM1/Mac1) and secretion of anti‐inflammatory cytokines (e.g., TGFβ), and initiate innate immune responses via transfer of Ags to APCs . In regard to adaptive immunity, LECs maintain naive and memory T‐cells, and support natural killer T‐cells (via secretion of IL‐7 and IL‐15, respectively) .…”

“…In regard to adaptive immunity, LECs maintain naive and memory T‐cells, and support natural killer T‐cells (via secretion of IL‐7 and IL‐15, respectively) . LECs also inhibit the overproliferation of differentiated and proliferating T‐cells through nitric oxide secretion . And similar to BECs, LECs have been suggested to have APC‐like properties as they express MHC I and II molecules on their surface.…”

CIMT 2018: Pushing frontiers in cancer immunotherapy — Report on the 16th Annual Meeting of the Association for Cancer Immunotherapy

“…Tumor-traversing lymphatic vessels are not just important for trafficking of immune activation signals to draining lymph nodes, but also promote the activation of immunosuppressive stromal cells. 25 For the latter reason, lymphangiogenesis is a marker for poor prognosis in human cancers. In accordance with this, B16-OVA (B16-OVA/VC) tumors expressing high levels of lymphangiogenic vascular endothelial growth factor (VEGF)-C grow more aggressively compared to B16-OVA.…”