Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
Cell Rep. 2021 May 11;35(6):109118. doi: 10.1016/j.celrep.2021.109118.
As a critical machinery for rapid pathogen removal, resident memory T cells (Ts) are locally generated after the initial encounter. However, their development accompanying tumorigenesis remains elusive. Using a murine breast cancer model, we show that Ts develop in the tumor, the contralateral mammary mucosa, and the pre-metastatic lung. Single-cell RNA sequencing of Ts reveals two phenotypically distinct populations representing their active versus quiescent phases. These Ts in different tissue compartments share the same TCR clonotypes and transcriptomes with a subset of intratumoral effector/effector memory T cells (Ts), indicating their developmental ontogeny. Furthermore, CXCL16 is highly produced by tumor cells and CXCR6 Ts are the major subset preferentially egressing the tumor to form distant Ts. Functionally, releasing CXCR6 retention in the primary tumor amplifies tumor-derived Ts in the lung and leads to superior protection against metastases. This immunologic fortification suggests a potential strategy to prevent metastasis in clinical oncology.
作为快速清除病原体的关键机制，驻留记忆 T 细胞（Ts）在初次接触后在局部产生。然而，它们在肿瘤发生过程中的发展仍然难以捉摸。使用小鼠乳腺癌模型，我们表明 Ts 在肿瘤、对侧乳腺黏膜和前转移肺中发育。Ts 的单细胞 RNA 测序揭示了两个表型上明显不同的群体，代表其活跃和静止阶段。这些来自不同组织隔室的 Ts 与肿瘤内效应器/效应记忆 T 细胞（Ts）的一部分具有相同的 TCR 克隆型和转录组，表明它们的发育发生。此外，CXCL16 由肿瘤细胞高度产生，CXCR6 Ts 是优先从肿瘤迁出形成远处 Ts 的主要亚群。在功能上，释放原发性肿瘤中 CXCR6 的保留可扩增肺中的肿瘤衍生 Ts，并导致对转移的更好保护。这种免疫强化提示了临床肿瘤学中预防转移的潜在策略。
