Colorectal cancer is a major cause of cancer-related death in Western countries and is associated with increased numbers of lymphatic vessels (LV) and tumor-associated macrophages (TAM). The VEGFC/VEGFR3 pathway is regarded as the principal inducer of lymphangiogenesis and it contributes to metastases; however, no data are available regarding its role during primary colorectal cancer development. We found that both VEGFC and VEGFR3 were upregulated in human nonmetastatic colorectal cancer, with VEGFR3 expressed on both LVs and TAMs. With the use of three different preclinical models of colorectal cancer, we also discovered that the VEGFC/VEGFR3 axis can shape both lymphatic endothelial cells and TAMs to synergistically inhibit antitumor immunity and promote primary colorectal cancer growth. Therefore, VEGFR3-directed therapy could be envisioned for the treatment of nonmetastatic colorectal cancer.

Activation of the VEGFC/VEGFR3 pathway induces tumor immune escape in colorectal cancer

Mazzone M.;
2019-01-01

Abstract

Colorectal cancer is a major cause of cancer-related death in Western countries and is associated with increased numbers of lymphatic vessels (LV) and tumor-associated macrophages (TAM). The VEGFC/VEGFR3 pathway is regarded as the principal inducer of lymphangiogenesis and it contributes to metastases; however, no data are available regarding its role during primary colorectal cancer development. We found that both VEGFC and VEGFR3 were upregulated in human nonmetastatic colorectal cancer, with VEGFR3 expressed on both LVs and TAMs. With the use of three different preclinical models of colorectal cancer, we also discovered that the VEGFC/VEGFR3 axis can shape both lymphatic endothelial cells and TAMs to synergistically inhibit antitumor immunity and promote primary colorectal cancer growth. Therefore, VEGFR3-directed therapy could be envisioned for the treatment of nonmetastatic colorectal cancer.
2019
79
16
4196
4210
Animals; Cancer Vaccines; Colorectal Neoplasms; Female; Humans; Lymphatic Vessels; Macrophages; Male; Mice, Inbred BALB C; Mice, Inbred C57BL; Neoplasms, Experimental; Vascular Endothelial Growth Factor C; Vascular Endothelial Growth Factor Receptor-3; Tumor Escape
Tacconi C.; Ungaro F.; Correale C.; Arena V.; Massimino L.; Detmar M.; Spinelli A.; Carvello M.; Mazzone M.; Oliveira A.I.; Rubbino F.; Garlatti V.; Spano S.; Lugli E.; Colombo F.S.; Malesci A.; Peyrin-Biroulet L.; Vetrano S.; Danese S.; D'Alessio S.
File in questo prodotto:
File Dimensione Formato  
41.pdf

Accesso riservato

Tipo di file: PDF EDITORIALE
Dimensione 2.14 MB
Formato Adobe PDF
2.14 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1840941
Citazioni
  • ???jsp.display-item.citation.pmc??? 24
  • Scopus 37
  • ???jsp.display-item.citation.isi??? 37
social impact