Heterogeneity of tumor lymphangiogenesis: Progress and prospects

Luo, Jincai

doi:10.1111/cas.13738

Cited by 19 publications

(14 citation statements)

References 75 publications

(146 reference statements)

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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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“…The remodelling of regional LVs to facilitate tumour cell dissemination plays an important pro-metastatic role in solid tumours, especially in cervical squamous cell carcinoma (CSCC) [6]. However, recent studies suggest that LVs are heterogeneous in their differential response to various micro-environmental signals and thus display distinct phenotypes and functions, which hinder their application in diagnosis and targeted therapy [7]. Different LV populations that secrete distinct profiles of cytokines have been identified in a variety of cancers [8].…”

Section: Introductionmentioning

confidence: 99%

A novel lymphatic pattern promotes metastasis of cervical cancer in a hypoxic tumour-associated macrophage-dependent manner

et al. 2021

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Lymphatic remodelling in the hypoxic tumour microenvironment (TME) is critically involved in the metastasis of cervical squamous cell carcinoma (CSCC); however, its underlying mechanisms remain unclear. Here, we uncovered a novel lymphatic pattern in the hypoxic TME, wherein lymphatic vessels (LVs) are encapsulated by tumour-associated macrophages (TAMs) to form an interconnected network. We describe these aggregates as LVEM (LVs encapsulated by TAMs) considering their advantageous metastatic capacity and active involvement in early lymph node metastasis (LNM). Mechanistic investigations revealed that interleukin-10 (IL-10) derived from hypoxic TAMs adjacent to LVs was a prerequisite for lymphangiogenesis and LVEM formation through its induction of Sp1 upregulation in lymphatic endothelial cells (LECs). Interestingly, Sp1high LECs promoted the transactivation of C–C motif chemokine ligand 1 (CCL1) to facilitate TAM and tumour cell recruitment, thereby forming a positive feedback loop to strengthen the LVEM formation. Knockdown of Sp1 or blockage of CCL1 abrogated LVEM and consequently attenuated LNM. Notably, CSCCnon-LNM is largely devoid of hypoxic TAMs and the resultant LVEM, which might explain its metastatic delay. These findings identify a novel and efficient metastasis-promoting lymphatic pattern in the hypoxic TME, which might provide new targets for anti-metastasis therapy and prognostic assessment.

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“…It has been well established that lymphangiogenesis can occur in and around tumors ( 23 ). However, the functional significance of intratumoral and peritumoral lymphatics involved in the pathology of tumors remains controversial.…”

Section: Discussionmentioning

confidence: 99%

Detection and prognostic value of intratumoral and peritumoral lymphangiogenesis in colorectal cancer

Zhang¹,

Liu²,

Shen³

et al. 2020

Transl Cancer Res TCR

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Background: Colorectal cancer (CRC) with lymphatic invasion is one of the critical prognostic factors in lymph node metastasis. Lymphangiogenesis has a significant effect on lymphatic metastasis and tumor progression. However, the significance of intratumoral and peritumoral lymphangiogenesis has been controversial in CRC. The aim of this study is to investigate the different role of introtumoral and peritumoral lymphangiogenesis in CRC progression and prognosis.Methods: Lymphangiogenesis of 120 CRC specimens, as measured by lymphatic vessel density (LVD), was examined by immunostaining for podoplanin, a lymphatic vessel-specific marker. The mean number of lymphatic vessels of three hotspots was measured in intratumoral and peritumoral areas as intratumoral LVD (LVDit) and peritumoral LVD (LVDpt), respectively. The association of LVDit and LVDpt with the clinicopathological findings and prognosis was investigated.Results: Compared to the peritumoral lymphatics, the intratumoral lymphatics were small, collapsed and irregular. The mean LVDpt was higher than the mean LVDit (P<0.001). LVDit was positively correlated with tumor size (P=0.009), tumor histologic grade (P=0.023), and overall survival (P=0.036). LVDpt was correlated with lymph node metastasis (P<0.001), tumor stage (P=0.004), and overall survival (P=0.016).Conclusions: LVDpt plays a prominent role in lymph node metastasis, whereas LVDit is more closely correlated with tumor growth and histopathological differentiation. Both LVDpt and LVDit contribute to CRC progression and prognosis.

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Heterogeneity of tumor lymphangiogenesis: Progress and prospects

Cited by 19 publications

References 75 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

A novel lymphatic pattern promotes metastasis of cervical cancer in a hypoxic tumour-associated macrophage-dependent manner

Detection and prognostic value of intratumoral and peritumoral lymphangiogenesis in colorectal cancer

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