Correlation with lymphocyte infiltration, but lack of prognostic significance of MECA-79-positive high endothelial venules in primary malignant melanoma

Abstract

High endothelial venules (HEVs) are specialized vessels in lymphoid organs, supporting lymphocyte trafficking from the blood. As the presence of these vessels was described recently in tumors, it was proposed that they could facilitate the development of antitumor immune response, resulting in improved prognosis. The aim of our study was to analyze the correlation of the density of HEVs with that of the different immune cell types as well as with the clinicopathologic parameters and the disease outcomes in patients with cutaneous melanoma. Primary melanoma samples of 118 patients were analyzed retrospectively by immunohistochemical labeling and quantitation of vessels stained with the MECA-79 antibody, as well as a panel of eight different immune cell types (CD8 and CD45RO T cells, lymphocytes expressing the CD25, CD134, or CD137 activation markers, FOXP3 regulatory T cells, CD20 B cells, and DC-LAMP mature dendritic cells). Correlations of MECA-79 vessel density with that of the immune cells, as well as with clinicopathologic parameters and disease outcomes were evaluated. We showed that the number of MECA-79 vessels correlates strongly with the peritumoral density of B and T lymphocytes. Moreover, higher HEV numbers were detected in tumors hosting tertiary lymphoid structures as well as in those of axial location compared with the ones in the extremity and in men compared with women, whereas no association was found with patient age, tumor thickness, histologic type or ulceration, or with the survival of melanoma patients. The density of MECA-79 HEVs in primary melanomas shows a correlation with B and T-lymphocyte density and differences according to the presence of tertiary lymphoid structures, tumor site, and the sex of the patient. However, it has no prognostic value.

High endothelial venules (HEVs) in immunity, inflammation and cancer

“…Our initial observations showing the strong correlation between the density of MECA-79 + TA-HEVs and densities of tumor-infiltrating CD3 + T cells, CD8 + T cells, and CD20 + B cells in primary breast cancer and melanoma [ 28 , 29 ], have been confirmed in many studies and extended to multiple human malignancies (Table 3 ). The density of MECA-79 + TA-HEVs is positively correlated with clinical parameters indicative of reduced tumor progression and invasion in primary melanoma [ 29 , 246 , 247 ] and with increased metastasis-free survival and overall survival in primary breast cancer [ 28 ]. MECA-79 + TA-HEVs are also associated with increased lymphocyte infiltration, progression free-survival and overall survival in head and neck cancer [ 248 – 250 ].…”

“…Indeed, MECA-79 + TA-HEVs are often found in T-cell rich areas containing DCs but no B cell follicles (Fig. 6 b) [ 29 , 247 , 253 , 256 , 262 ]. These structures enriched in T cells and DCs, that are highly similar to the T-cell zones of lymphoid tissues, may provide a supportive niche for CD8 + T cells in human tumors [ 312 ].…”

Prediction of relapse in stage I testicular germ cell tumor patients on surveillance: investigation of biomarkers

“…However, none has been introduced in the clinic yet, possibly since results among studies were not consistent or reflecting the variability among study designs. MECA-79 is another biomarker shown to be involved in antitumor responses in some malignancies, although so far not been explored in testicular germ cell tumors [ 23 – 25 ]. Also, for TEX19, a cancer testis antigen present in normal adult testis and involved in proliferation of several cancer types and of germ cells [ 26 ], its expression profile in testicular germ cell tumors has not been demonstrated yet.…”

Tertiary lymphoid structures in cancer: immune mechanisms and clinical implications

“…In cutaneous melanoma, HEV is mainly found within TLS structures and its density is strongly correlated with the density of T and B cells. 126 Of interest, Eschweiler et al 127 pointed out that a new cell subset located primarily in TLS, follicular regulatory T cells (Tfr), exerts a stronger suppressive effect than Tregs. Furthermore, anti-CTLA-4 therapy to deplete Tfr cells followed by anti-PD-1 therapy strengthens ICB efficacy, thus resulting in better clinical outcomes.…”