The Interplay Between Lymphatic Vessels and Chemokines

Farnsworth, Rae H.; Karnezis, Tara; Maciburko, Simon J; Mueller, Scott N.; Stacker, Steven A.

doi:10.3389/fimmu.2019.00518

Cited by 59 publications

(64 citation statements)

References 163 publications

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“…There is no data regarding the interaction of CLR with key factors that are thought to promote lymphatic metastasis, including members of the vascular endothelial growth factor (VEGF) secreted glycoproteins, as well as insulin and hepatocyte growth factors (77–79). Several cytokines, including CCL21 through the activation of CCR7 (80, 81), CCL5 and CXCL10 (82), have been implicated in metastatic lymphangiogenesis as well as the formation and maintenance of CLR and other tumor-specific immune responses.…”

Section: Introductionmentioning

confidence: 99%

The Crohn's-Like Lymphoid Reaction to Colorectal Cancer-Tertiary Lymphoid Structures With Immunologic and Potentially Therapeutic Relevance in Colorectal Cancer

2019

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The Crohn's-like lymphoid reaction (CLR) to colorectal cancer (CRC), a CRC-specific ectopic lymphoid reaction, is thought to play an important role in the host response to CRC. CLR is characterized by peritumoral lymphocytic aggregates that are found at the advancing edge of the tumor. Spatial and molecular characterization of CLR within the tumor microenvironment (TME) have uncovered a spectrum of peritumoral lymphoid aggregates with varying levels of organization and maturation. In early stages of CLR development, CD4+ T-cells cluster predominantly with mature antigen presenting dendritic cells. As CLR matures, increasing numbers of B-cells, as well as follicular dendritic cells are recruited to create lymphoid follicles. When highly organized, CLR resembles functional tertiary lymphoid structures (TLS), allowing for lymphocyte recruitment to the TME and promoting a tumor-specific adaptive immune response. CLR has been consistently associated with favorable prognostic factors and improved survival among CRC patients, often providing more prognostic information than current clinical staging systems. However, consensus is lacking regarding CLR scoring and it is not clinically assessed or reported. Differences between CLR and other cancer-associated lymphoid structures exist both in primary and metastatic disease, underscoring the need to characterize organ-specific TLS. Further research is needed to explore the role of CLR in predicting response to immunotherapy and to leverage CLR to promote immunotherapeutic strategies in CRC.

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Section: Introductionmentioning

confidence: 99%

The Crohn's-Like Lymphoid Reaction to Colorectal Cancer-Tertiary Lymphoid Structures With Immunologic and Potentially Therapeutic Relevance in Colorectal Cancer

2019

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“…Portal hypertension related to biliary fibrosis in rats causes extensive mast cell infiltration of the mesenteric lymph complex (MLC) [36]. This massive recruitment [38]. In this way, the hypothesis that the mesenteric-lymphatic collateral circulation is developed through the incidence of two consecutive hits in portal hypertensive rats could be proposed.…”

Section: Discussionmentioning

confidence: 99%

“…In this way, the hypothesis that the mesenteric-lymphatic collateral circulation is developed through the incidence of two consecutive hits in portal hypertensive rats could be proposed. The first hit would be related to the inflammation produced by portal hypertension, with edema and lymphatic flow increase, while the second hit would be the intestinal lymphatic hypertension, which in turn favor lymphangiogenesis and mesenteric adenitis [38]. Hence, either intestinal angiogenesis or lymphangiogenesis in portal hypertension would have a complementary etiopathogenic role [39].…”

Section: Discussionmentioning

confidence: 99%

Gut Lymphangiopathy: Adding Fuel to the Fire in Chronic Liver Disease

Tresierra¹,

Aller²,

Prieto³

et al. 2019

ABB

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The splanchnic inflammation inchronic liver disease increases intestinal angiogenesis. In the current study our aim was demonstrating that the small bowel lymphangiogenesis is associated with angiogenesis in chronic cholestasis in the rat. A stereological study of the lymphatic microcirculation in the small intestine was performed in cholestatic rats. Portal enteropathy in cholestasis increases lymphatic microvessels in the mucosa and submucosa layers. Thus, the lymphatic microvessel volume fraction was superior (p < 0.001) in the mucosa (0.16 ± 0.01) and submucosa (0.16 ± 0.01), in regard to the muscle layer 0.015 ± 0.01. The lymphatic microvessel length density was higher in the mucosa (76.89 ± 2.86 mm −2 ; p < 0.001) and submucosa (14.87 ± 2.86 mm −2 ; p < 0.01), in relationship to the muscle layer (5.04 ± 2.92 mm −2 ). These alterations predominate in the duodenum (volume fraction: 0.10 ± 0.01 and length density: 33.55 ± 5.98 mm −2 ) and ileum (volume fraction: 0.16 ± 0.01 and length density: 38.62 ± 6.07 mm −2 ). This study demonstrates the predominance of an increased lymphangiogenic response in both end sides of the small bowel associated with chronic liver disease. Since the porto-systemic venous collateral circulation in the chronic liver insufficiency is developed in the ends of the gastrointestinal tract, the excessive duodeno-ileal lymphangiogenesis could suggest the development of amesenteric-systemic lymphatic bypass in the chronic portal hypertension.

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“…An example is high expression of CCR7 found in various human cancer cells [53][54][55]. C-C chemokine ligand 21 (CCL21), the ligand for CCR7, is constitutively expressed by lymphatic vessels and in secondary lymphoid organs [56] and can be upregulated in response to increased lymphatic flow and inflammatory stimuli [57]. Likewise, lymphatic vessel derived CXCL12 in physiological systems directs dendritic cell migration to lymph nodes [58].…”

Section: Cancer Cells Use Existing Migratory Cuesmentioning

confidence: 99%

Parallels of Resistance between Angiogenesis and Lymphangiogenesis Inhibition in Cancer Therapy

Jones

2020

Cells

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Metastasis is the primary cause of cancer-related mortality. Cancer cells primarily metastasize via blood and lymphatic vessels to colonize lymph nodes and distant organs, leading to worse prognosis. Thus, strategies to limit blood and lymphatic spread of cancer have been a focal point of cancer research for several decades. Resistance to FDA-approved anti-angiogenic therapies designed to limit blood vessel growth has emerged as a significant clinical challenge. However, there are no FDA-approved drugs that target tumor lymphangiogenesis, despite the consequences of metastasis through the lymphatic system. This review highlights several of the key resistance mechanisms to anti-angiogenic therapy and potential challenges facing anti-lymphangiogenic therapy. Blood and lymphatic vessels are more than just conduits for nutrient, fluid, and cancer cell transport. Recent studies have elucidated how these vasculatures often regulate immune responses. Vessels that are abnormal or compromised by tumor cells can lead to immunosuppression. Therapies designed to improve lymphatic vessel function while limiting metastasis may represent a viable approach to enhance immunotherapy and limit cancer progression.

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The Interplay Between Lymphatic Vessels and Chemokines

Cited by 59 publications

References 163 publications

The Crohn's-Like Lymphoid Reaction to Colorectal Cancer-Tertiary Lymphoid Structures With Immunologic and Potentially Therapeutic Relevance in Colorectal Cancer

The Crohn's-Like Lymphoid Reaction to Colorectal Cancer-Tertiary Lymphoid Structures With Immunologic and Potentially Therapeutic Relevance in Colorectal Cancer

Gut Lymphangiopathy: Adding Fuel to the Fire in Chronic Liver Disease

Parallels of Resistance between Angiogenesis and Lymphangiogenesis Inhibition in Cancer Therapy

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