AIMS: Tumour-infiltrating lymphocytes have prognostic value in malignant melanoma. High endothelial venules (HEVs) are specialized vessels present in lymph nodes and tertiary lymphoid organs. CCL19, CCL21 and CCR7 regulate lymphocyte migration through HEVs. The aim of our study was to correlate HEV density in cutaneous primary and metastatic malignant melanomas with clinicopathological parameters, and with CCL19, CCL21 and CCR7 mRNA expression. METHODS AND RESULTS: High endothelial venule density was evaluated by immunohistochemistry with a specific antibody, MECA-79, and chemokine expression was evaluated by real-time PCR. MECA-79-positive vessels, covered by cuboidal (C-HEV) or flat (F-HEV) endothelium, were detected in 55% of melanomas. HEV density was higher in primary melanomas than in metastases. Positive correlations were found between C-HEV density and lymphocytic infiltration, and between F-HEV density and tumour regression. Cases in which the number of C-HEVs exceeded that of F-HEVs had higher levels of CCL19, CCL21, and CCR7. CONCLUSIONS: Our results support a predominant role for C-HEV in the recruitment of lymphocytes in cutaneous melanomas, mediated by CCL19 and CCL21, whereas the density of F-HEV strongly correlates with tumour regression, Therefore, cuboidal and flat HEVs may serve as indicators of the active and late quiescent phases, respectively, of tumour regression in cutaneous malignant melanoma.
AIMS: Tumour-infiltrating lymphocytes have prognostic value in malignant melanoma. High endothelial venules (HEVs) are specialized vessels present in lymph nodes and tertiary lymphoid organs. CCL19, CCL21 and CCR7 regulate lymphocyte migration through HEVs. The aim of our study was to correlate HEV density in cutaneous primary and metastatic malignant melanomas with clinicopathological parameters, and with CCL19, CCL21 and CCR7 mRNA expression. METHODS AND RESULTS: High endothelial venule density was evaluated by immunohistochemistry with a specific antibody, MECA-79, and chemokine expression was evaluated by real-time PCR. MECA-79-positive vessels, covered by cuboidal (C-HEV) or flat (F-HEV) endothelium, were detected in 55% of melanomas. HEV density was higher in primary melanomas than in metastases. Positive correlations were found between C-HEV density and lymphocytic infiltration, and between F-HEV density and tumour regression. Cases in which the number of C-HEVs exceeded that of F-HEVs had higher levels of CCL19, CCL21, and CCR7. CONCLUSIONS: Our results support a predominant role for C-HEV in the recruitment of lymphocytes in cutaneous melanomas, mediated by CCL19 and CCL21, whereas the density of F-HEV strongly correlates with tumour regression, Therefore, cuboidal and flat HEVs may serve as indicators of the active and late quiescent phases, respectively, of tumour regression in cutaneous malignant melanoma.
Authors: Beth A Helmink; Sangeetha M Reddy; Jianjun Gao; Shaojun Zhang; Rafet Basar; Rohit Thakur; Keren Yizhak; Moshe Sade-Feldman; Jorge Blando; Guangchun Han; Vancheswaran Gopalakrishnan; Yuanxin Xi; Hao Zhao; Rodabe N Amaria; Hussein A Tawbi; Alex P Cogdill; Wenbin Liu; Valerie S LeBleu; Fernanda G Kugeratski; Sapna Patel; Michael A Davies; Patrick Hwu; Jeffrey E Lee; Jeffrey E Gershenwald; Anthony Lucci; Reetakshi Arora; Scott Woodman; Emily Z Keung; Pierre-Olivier Gaudreau; Alexandre Reuben; Christine N Spencer; Elizabeth M Burton; Lauren E Haydu; Alexander J Lazar; Roberta Zapassodi; Courtney W Hudgens; Deborah A Ledesma; SuFey Ong; Michael Bailey; Sarah Warren; Disha Rao; Oscar Krijgsman; Elisa A Rozeman; Daniel Peeper; Christian U Blank; Ton N Schumacher; Lisa H Butterfield; Monika A Zelazowska; Kevin M McBride; Raghu Kalluri; James Allison; Florent Petitprez; Wolf Herman Fridman; Catherine Sautès-Fridman; Nir Hacohen; Katayoun Rezvani; Padmanee Sharma; Michael T Tetzlaff; Linghua Wang; Jennifer A Wargo Journal: Nature Date: 2020-01-15 Impact factor: 69.504