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

被引：57

作者：

Bordry, Natacha ^{[1
,2
,3
,4
]}

Broggi, Maria A. S. ^{[3
,4
,11
]}

de Jonge, Kaat ^{[1
,2
]}

Schaeuble, Karin ^{[1
,2
]}

Gannon, Philippe O. ^{[5
,6
]}

Foukas, Periklis G. ^{[5
,6
,10
]}

Danenberg, Esther ^{[5
,6
]}

Romano, Emanuela ^{[5
,6
,8
]}

Baumgaertner, Petra ^{[5
,6
]}

Fankhauser, Manuel ^{[3
,4
]}

Wald, Noemie ^{[1
,2
]}

Cagnon, Laurene ^{[5
,6
]}

Abed-Maillard, Samia ^{[5
,6
]}

Maby-El Hajjami, Helene ^{[1
,2
]}

Murray, Timothy ^{[1
,2
]}

Ioannidou, Kalliopi ^{[1
,2
]}

Letovanec, Igor ^{[7
]}

Yan, Pu ^{[7
]}

Michielin, Olivier ^{[5
,6
]}

Matter, Maurice ^{[5
,6
,10
]}

Swartz, Melody A. ^{[3
,4
,9
]}

Speiser, Daniel E. ^{[1
,2
,5
,6
]}

机构：

[1] Univ Lausanne UNIL, Clin Tumor Biol & Immunotherapy Grp, Dept Oncol, Lausanne, Switzerland

[2] Univ Lausanne UNIL, Ludwig Canc Res, Lausanne, Switzerland

[3] Ecole Polytech Fed Lausanne, Inst Bioengn, Sch Life Sci, Lausanne, Switzerland

[4] Ecole Polytech Fed Lausanne, Swiss Inst Expt Canc Res ISREC, Sch Life Sci, Lausanne, Switzerland

[5] Lausanne Univ Hosp Ctr CHUV, Dept Oncol, Lausanne, Switzerland

[6] Univ Lausanne, Lausanne, Switzerland

[7] CHU Vaudois, Dept Pathol, Lausanne, Switzerland

[8] Inst Curie, INSERM, U932, Dept Oncol, Paris, France

[9] Univ Athens, Attikon Univ Hosp, Dept Pathol 2, Athens, Greece

[10] CHU Vaudois, Dept Surg, Lausanne, Switzerland

[11] Univ Chicago, Inst Mol Engn, Chicago, IL 60637 USA

来源：

ONCOIMMUNOLOGY | 2018年 / 7卷 / 08期

基金：

欧洲研究理事会; 瑞士国家科学基金会;

关键词：

Immunotherapy; lymphatics; tumor immunology; T cell inhibition; T cell promotion; GROWTH FACTOR-C; PRIMARY CUTANEOUS MELANOMA; PROMOTES TUMOR-METASTASIS; MALIGNANT-MELANOMA; ENDOTHELIAL-CELLS; ADOPTIVE IMMUNOTHERAPY; CANCER-IMMUNOTHERAPY; MICROVESSEL DENSITY; INTERSTITIAL FLOW; NODE METASTASIS;

D O I：

10.1080/2162402X.2018.1462878

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

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-dioxygenase (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.

引用

页数：13

共 71 条

[1] The density and type of MECA-79-positive high endothelial venules correlate with lymphocytic infiltration and tumour regression in primary cutaneous melanoma [J].