Activation of the VEGFC/VEGFR3 Pathway Induces Tumor Immune Escape in Colorectal Cancer

Tacconi, Carlotta; Ungaro, Federica; Correale, Carmen; Arena, Vincenzo; Massimino, Luca; Detmar, Michael; Spinelli, Antonino; Carvello, Michele; Mazzone, Massimiliano; Oliveira, Ana I.; Rubbino, Federica; Garlatti, Valentina; Spanò, Salvatore; Lugli, Enrico; Colombo, Federico; Malesci, Alberto; Peyrin–Biroulet, Laurent; Vetrano, Stefania; Danese, Silvio; D’Alessio, Silvia

doi:10.1158/0008-5472.can-18-3657

Cited by 61 publications

(51 citation statements)

References 48 publications

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“…Similar to VEG-FR-1 and VEGFR-2, VEGFR-3 is a member of the VEGF family. As a membrane-anchored tyrosine kinase and VEGF receptor, VEGFR-3 plays a crucial role in lymphangiogenesis [4]. However, the relatively specific anchorage of VEGFR-3 on LECs occurs at the late stage of lymphatic development.…”

Section: Introductionmentioning

confidence: 99%

Lymphatic Vessels Enhancing Adaptive Immunity Deteriorates Renal Inflammation and Renal Fibrosis

Pei

Zeng

et al. 2020

Kidney Dis

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Background: Lymphatic vessels transport lymph away from microvascular beds into the cardiovascular system. The basic function of the lymphatic system include absorption of wa ter and macromolecules in the interstitial fluid, which plays an important role in maintaining osmotic balance of the body. Recent studies have shown that lymphangiogenesis is associated with tumor metabolism, injury repair, and chron ic inflammation, and deteriorates disease progression via immune cell trafficking. Summary: Renal interstitial lymph angiogenesis is found in patients with chronic kidney dis ease and a series of animal models of renal fibrosis. Lymphat ic vessels transfer antigen and antigenpresenting cells from peripheral tissues to lymph nodes, which initiates adaptive immunity and in turn deteriorates renal inflammation and renal fibrosis, even in nonautoimmune renal diseases. Key Messages: This review summarizes the latest findings on how lymphatics participate in the progression of chronic kid ney disease. This discussion will serve to highlight the role of adaptive immunity in noninfectious and nonautoimmune nephropathy, in order to provide new ideas and methods for prevention and treatment of kidney diseases.

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Section: Introductionmentioning

confidence: 99%

Lymphatic Vessels Enhancing Adaptive Immunity Deteriorates Renal Inflammation and Renal Fibrosis

Pei

Zeng

et al. 2020

Kidney Dis

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“…and Th17, CTLs and NK cells [46][47][48][49]. Similarly, VEGFC/VEGFR3 signaling closely connected with LINC01116 and LINC00460 were mainly expressed on immune cells including macrophages and NK cells, and might also disturb ICB e cacy via affecting dendritic cells and CD8 T cells [50][51][52], or inducing the naïve T cells via CCL21 [53].…”

Section: Discussionmentioning

confidence: 99%

Identification of an Immune-related Seven-lncRNA Signature Predicting Prognosis and Tumor-infiltrating Immune Cells in Lung Adenocarcinoma

Mou

Zhang

et al. 2020

Preprint

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Background: Lung adenocarcinoma (LUAD) is a common cancer. Immunotherapy is one of the major treatments but showing diverse efficacy in LUAD. Long non-coding RNAs (lncRNAs) are emerging as important players in immune regulation in cancer. Herein, we identified and validated a prognostic signature of immune-related lncRNAs in LUAD and explored its correlation with tumor-infiltrating immune cells (TIICs) by bioinformatics analysis.Methods: Immune-related lncRNAs were acquired using Pearson correlation analysis between lncRNAs from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and immune genes from the ImmPort website and Molecular Signatures Database. The risk signature was constructed in the TCGA group through univariable Cox, lasso and multivariable Cox regression analyses. The prognostic value of the established risk signature was validated in both TCGA and GEO datasets. The interacted TIICs and immune pathways with each single lncRNA and the risk signature were investigated respectively in ImmLnc database, Cibersortx database and gene set enrichment analysis (GSEA) analyses.Results: A seven immune-related lncRNAs prognostic signature was constructed and it stratified LUAD into high and low risk groups. High risk group showed poorer overall survival (OS) in comparison with low risk group via survival analysis.The seven-lncRNAs signature was closely correlated with various TIICs and immune pathways mostly involved in T cell activation, antigen processing and presentation, chemokines and cytokine receptors.Conclusions: The seven lncRNAs model was identified as a predictable signature for prognosis of LUAD patients probably due to its immunomodulation role. This study might provide a new target for enhancing the efficacy of immunotherapy in this mortal disease.

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“…Emerging evidence indicates that VEGF‐C can modulate the immune system to facilitate tumor cells to more easily escape immune surveillance . In addition, PD‐L1 can also promote tumor cells to escape from host immune attack .…”

Section: Discussionmentioning

confidence: 99%

“…Tacconi et al . reported VEGFC could enhance tumor growth via fostering cancer immune escape . Lund et al .…”

Section: Introductionmentioning

confidence: 99%

Clinical importance of VEGFC and PD‐L1 co‐expression in lung adenocarcinoma patients

et al. 2020

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Background: Vascular endothelial growth factor C (VEGFC), an activator of lymphangiogenesis, is newly identified as an immunomodulator which can regulate the immune system so that tumor cells more easily escape immune surveillance. Evidence has shown programmed cell death-ligand 1 (PD-L1) can also suppress the immune response. Nevertheless, the clinical significance of coexpression of VEGFC and PD-L1 for predicting outcomes in patients with lung adenocarcinoma has not yet been determined. Methods: A total of 114 patients with lung adenocarcinoma who underwent surgeries at were retrospectively reviewed. Tissue specimens were collected for immunohistochemistry of VEGFC and PD-L1 which were analyzed with an H-score system. Results: In this study, 57 (50.0%) and 47 (41.2%) patients were classified as VEGFC high expression and PD-L1 high expression. Co-expression was observed in 33 (28.9%) patients. In addition, a positive correlation was found between VEGFC and PD-L1 (P = 0.0398, r = 0.1937). In a univariate analysis, both progression-free survival (PFS) and overall survival (OS) were significantly worse in the VEGFC high expression group and the PD-L1 high expression group, respectively. Furthermore, VEGFC/PD-L1 co-expression showed a worse OS (P = 0.03) and PFS survival (P = 0.01) than the other groups. Conclusions: Taken together, these results indicate that VEGFC/PD-L1 coexpression can forecast both poor OS and PFS in patients with resected lung adenocarcinoma. Co-expression of VEGFC and PD-L1 may serve as a significant prognostic factor for patients with lung adenocarcinoma. Key pointsVEGFC/PD-L1 co-expression forecasts poor survival in patients with resected lung adenocarcinoma. VEGFC/PD-L1 co-expression may be used as a prognostic indicator and provide the theoretical possibility to screen the optimal population with a combination of anti-VEGFC and anti-PD-L1 therapy in the clinical treatment.

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Activation of the VEGFC/VEGFR3 Pathway Induces Tumor Immune Escape in Colorectal Cancer

Cited by 61 publications

References 48 publications

Lymphatic Vessels Enhancing Adaptive Immunity Deteriorates Renal Inflammation and Renal Fibrosis

Lymphatic Vessels Enhancing Adaptive Immunity Deteriorates Renal Inflammation and Renal Fibrosis

Identification of an Immune-related Seven-lncRNA Signature Predicting Prognosis and Tumor-infiltrating Immune Cells in Lung Adenocarcinoma

Clinical importance of VEGFC and PD‐L1 co‐expression in lung adenocarcinoma patients

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