High endothelial venules in intracranial germinomas: Implications for lymphocytes infiltration

Abstract

BackgroundReactive lymphocytes are substantial components of germinoma, which are believed to be related to the favorable prognosis of this intracranial tumor and better response to immunotherapy. However, the mechanisms managing the recruitment of lymphocytes are poorly understood. High endothelial venules (HEVs) are specialized blood vessels that play key roles in lymphocyte tra cking in Lymph nodes. These vessels are associated with lymphocytes in ltration in chronic in ammatory diseases and various malignant tumors, but their distribution and implications in germinoma are unknown. MethodsThis study investigated the presence and distribution of HEVs in 42 germinomas by immunohistochemical staining of peripheral node addressin (PNAd) and transmission electron microscopic examination. The correlation of the densities of HEVs with the extent of T and B lymphocytes in ltration and several clinicopathological characteristics were also analyzed to determine whether HEVs are responsible for lymphocytes recruitment and their roles in anti-tumor immunity in germinoma. ResultsPNAd-positive HEVs were detected in 31% (13/42) of germinomas, and their presence correlated with abundant in ltrating CD3 + T cells, CD20 + B cells and CD8 + Cytotoxic T Lymphocytes (p = 0.0410, 0.0023, 0.0061, respectively). Higher HEVs density was also correlated with several clinicopathological parameters, which are recognized indicators for favorable prognosis in germinomas, including typical tumor location (p = 0.0093), lower tumor cell content (P = 0.0428), and younger age at diagnosis (p = 0.0121). Furthermore, bioinformatics analysis showed HEVs-associated genes mainly enriched in immune-related Gene Ontology terms, including innate immune response, in ammatory response, and B cell receptor signaling pathway. The xCell analysis revealed that germinomas with higher HEVs enrichment scores had increased levels of the immune score, microenvironment score, dendritic cells, CD8 + central memory T-cells, CD4 + memory T-cells, and B-cells. ConclusionOur ndings indicate that HEVs could contribute to lymphocytes recruitment in germinomas, thus may serve as a predictor of favorable prognosis and better response to immunotherapy in this intracranial tumor.

Advances in genetic abnormalities, epigenetic reprogramming, and immune landscape of intracranial germ cell tumors

“…The presence of HEVs was associated with abundant infiltration of CD3+T, CD20+B, and CD8+T cells. Higher HEV levels were associated with a favorable prognosis for germinomas [ 1 ]. Takami et al found that NGGCTs had significantly higher levels of immune cell infiltration compared to germinomas in their transcriptomic study [ 31 ].…”