淋巴细胞是免疫观测肿瘤的关键，但我们对促进淋巴细胞抗癌功能的空间组织和物理相互作用的理解有限。我们使用多重成像、定量空间分析和机器学习，创建了Kras/Trp53基因突变小鼠模型和人类切除肺肿瘤的高清地图。相互作用的淋巴细胞网络（“淋巴网”）成为抗癌免疫反应的独特特征。淋巴网从小T细胞集群核化并逐渐包括B细胞。CXCR3介导的修复调节淋巴网的大小和数量，但T细胞抗原表达指导肿瘤内部定位。淋巴网优先寄居着TCF1+ PD-1+祖细胞CD8+ T细胞，参与免疫检查点阻断（ICB）疗法的反应。治疗小鼠ICB或抗原靶向疫苗后，淋巴网保留祖细胞并增加细胞毒性CD8+ T细胞群体，可能通过祖细胞分化实现。这些数据表明，淋巴网创建了一个有利于CD8+ T细胞抗肿瘤反应的空间环境。版权所有© 2023年作者。由Elsevier Inc.发表，版权所有。

Lymphocytes are key for immune surveillance of tumors, but our understanding of the spatial organization and physical interactions that facilitate lymphocyte anti-cancer functions is limited. We used multiplexed imaging, quantitative spatial analysis, and machine learning to create high-definition maps of lung tumors from a Kras/Trp53-mutant mouse model and human resections. Networks of interacting lymphocytes ("lymphonets") emerged as a distinctive feature of the anti-cancer immune response. Lymphonets nucleated from small T cell clusters and incorporated B cells with increasing size. CXCR3-mediated trafficking modulated lymphonet size and number, but T cell antigen expression directed intratumoral localization. Lymphonets preferentially harbored TCF1+ PD-1+ progenitor CD8+ T cells involved in responses to immune checkpoint blockade (ICB) therapy. Upon treatment of mice with ICB or an antigen-targeted vaccine, lymphonets retained progenitor and gained cytotoxic CD8+ T cell populations, likely via progenitor differentiation. These data show that lymphonets create a spatial environment supportive of CD8+ T cell anti-tumor responses.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.