头颈部鳞状细胞癌（HNSCCs）以大量从外周血液中招募的单核细胞和巨噬细胞为特征。然而，目前尚未确定这些浸润细胞是否能够携带与肿瘤相关的新生物标记物重返循环。本研究报告了一种成分蛋白为钙离子激活的Cl-通道（CaCCs）的BEST1，高度表达于HNSCC患者外周血液中的经典单核细胞。这是由于肿瘤细胞对单核细胞的教育，其中肿瘤血管内皮生长因子A通过MEK-ERK-ELK1途径上调了单核细胞上BEST1的表达。这导致更好的IL-6和IL-8分泌，从而促进了肿瘤细胞的增殖。这项工作还发现BEST1促进了单核细胞的活动性，有助于这些细胞的迁移重新进入循环。这些结果表明，外周单核细胞上BEST1的表达可能是一个监测肿瘤进展的潜在工具，并开辟了在单核细胞而不是在肿瘤或其产物上寻找癌症生物标记物的可能性。© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.

Head and neck squamous cell carcinomas (HNSCCs) are characterized by an abundance of monocytes and macrophages recruited from the peripheral blood. However, it has not been determined whether these infiltrated cells can be released back into circulation with a tumor-associated neobiosignature. This study reports that Bestrophin1 (BEST1), a component protein of Ca2+ -activated Cl- channels (CaCCs), is highly expressed on classical monocytes in the peripheral blood of HNSCC patients. This is due to monocyte education by tumor cells, in which tumoral VEGF-A upregulates BEST1 expression on monocytes through the MEK-ERK-ELK1 pathway. This leads to improved secretion of IL-6 and IL-8, which promotes tumor cell proliferation. This work also finds that BEST1 facilitates the motility of monocytes, contributing to the migration of these cells back into circulation. These results suggest that the expression of BEST1 on peripheral monocytes may be a potential tool for monitoring tumor progression, and opens up the possibility of searching for cancer biomarkers on monocytes rather than on the tumor or its products.© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.