Lymphatic vessel density is associated with CD8+ T cell infiltration and immunosuppressive factors in human melanoma

OncoImmunology

Pu Yan¹  Igor Letovanec¹  Maria A. S. Broggi²  Melody A. Swartz²  Manuel Fankhauser²  Laurène Cagnon³  Philippe O. Gannon³  Samia Abed-Maillard³  Maurice Matter³  Periklis G. Foukas³  Olivier Michielin³  Emanuela Romano³  Esther Danenberg³  Kaat de Jonge⁴  Noémie Wald⁴  Hélène Maby-El Hajjami⁴  Karin Schaeuble⁴  Petra Baumgaertner⁴  Daniel E. Speiser⁴  Natacha Bordry⁴  Timothy Murray⁴  Kalliopi Ioannidou⁴ 

[1]CHUV

[2]Institute of Bioengineering and Swiss Institute for Experimental Cancer Research (ISREC)

[3]Lausanne University Hospital Center (CHUV) and University of Lausanne

[4]University of Lausanne (UNIL)

关键词: immunotherapy;    lymphatics;    tumor immunology;    t cell inhibition;    t cell promotion;   

DOI  :  10.1080/2162402X.2018.1462878

来源: DOAJ

【 摘 要 】

Increased density of tumor-associated lymphatic vessels correlates with poor patient survival in melanoma and other cancers, yet lymphatic drainage is essential for initiating an immune response. Here we asked whether and how lymphatic vessel density (LVD) correlates with immune cell infiltration in primary tumors and lymph nodes (LNs) from patients with cutaneous melanoma. Using immunohistochemistry and quantitative image analysis, we found significant positive correlations between LVD and CD8+ T cell infiltration as well as expression of the immunosuppressive molecules inducible nitric oxide synthase (iNOS) and 2,3-dioxygénase (IDO). Interestingly, similar associations were seen in tumor-free LNs adjacent to metastatic ones, indicating loco-regional effects of tumors. Our data suggest that lymphatic vessels play multiple roles at tumor sites and LNs, promoting both T cell infiltration and adaptive immunosuppressive mechanisms. Lymph vessel associated T cell infiltration may increase immunotherapy success rates provided that the treatment overcomes adaptive immune resistance.

【 授权许可】

Unknown