Strong and durable anticancer immune responses are associated with the generation of activated cancer-specific T cells in the draining lymph nodes. However, cancer cells can colonize lymph nodes and drive tumour progression. Here, we show that lymphocytes fail to penetrate metastatic lesions in lymph nodes. In tissue from patients with breast, colon, and head and neck cancers, as well as in mice with spontaneously developing breast-cancer lymph-node metastases, we found that lymphocyte exclusion from nodal lesions is associated with the presence of solid stress caused by lesion growth, that solid stress induces reductions in the number of functional high endothelial venules in the nodes, and that relieving solid stress in the mice increased the presence of lymphocytes in lymph-node lesions by about 15-fold. Solid-stress-mediated impairment of lymphocyte infiltration into lymph-node metastases suggests a therapeutic route for overcoming T-cell exclusion during immunotherapy.

强烈而持久的抗癌免疫反应与引流淋巴结中活化的癌症特异性 T 细胞的产生有关。然而，癌细胞可以定殖淋巴结并推动肿瘤进展。在这里，我们表明淋巴细胞无法穿透淋巴结中的转移性病灶。在乳腺癌、结肠癌和头颈癌患者的组织中，以及在自发发生乳腺癌淋巴结转移的小鼠中，我们发现淋巴细胞从淋巴结病变中排除与病变引起的固体应力的存在有关生长，固体应力会导致淋巴结中功能性高内皮小静脉数量减少，并且减轻小鼠的固体应力会使淋巴结病变中淋巴细胞的存在增加约 15 倍。