外泌体是纳米大小的细胞外囊泡，已成为肿瘤细胞与免疫系统之间串扰的关键介质。细胞间粘附分子1（ICAM1）在多种免疫功能以及癌症的发生、发展和转移中发挥着至关重要的作用。作为一种在细胞膜上表达的糖蛋白，ICAM1 分泌到细胞外的外泌体上，调节免疫抑制微环境。然而，外泌体ICAM1在乳腺癌骨转移免疫微环境中的作用仍不清楚。本研究旨在阐明外泌体 ICAM1 在促进三阴性乳腺癌 (TNBC) 中 CD8 T 细胞耗竭和随后的骨转移中的作用。我们证明，TNBC 细胞释放富含 ICAM1 的外泌体，ICAM1 与其受体的结合对于 CD8 T 细胞增殖和功能的抑制作用是必要的。这种关键的参与不仅抑制 CD8 T 细胞增殖和激活，而且还启动有利于 TNBC 肿瘤生长和骨转移的免疫抑制微环境的发展。此外，ICAM1阻断显着损害肿瘤外泌体与CD8 T细胞结合的能力，从而抑制其免疫抑制作用。本研究阐明了原发性肿瘤与外泌体介导的免疫系统之间复杂的相互作用，并为开发针对 ICAM1 的新型癌症免疫疗法奠定了基础，旨在减轻 TNBC 骨转移。版权所有 © 2024 Elsevier Ltd. 所有权利预订的。

Exosomes, which are nanosized extracellular vesicles, have emerged as crucial mediators of the crosstalk between tumor cells and the immune system. Intercellular adhesion molecule 1 (ICAM1) plays a crucial role in multiple immune functions as well as in the occurrence, development and metastasis of cancer. As a glycoprotein expressed on the cell membrane, ICAM1 is secreted extracellularly on exosomes and regulates the immunosuppressive microenvironment. However, the role of exosomal ICAM1 in the immune microenvironment of breast cancer bone metastases remains unclear. This study aimed to elucidated the role of exosomal ICAM1 in facilitating CD8+ T cell exhaustion and subsequent bone metastasis in triple-negative breast cancer (TNBC). We demonstrated that TNBC cells release ICAM1-enriched exosomes, and the binding of ICAM1 to its receptor is necessary for the suppressive effect of CD8 T cell proliferation and function. This pivotal engagement not only inhibits CD8+ T cell proliferation and activation but also initiates the development of an immunosuppressive microenvironment that is conducive to TNBC tumor growth and bone metastasis. Moreover, ICAM1 blockade significantly impairs the ability of tumor exosomes to bind to CD8+ T cells, thereby inhibiting their immunosuppressive effects. The present study elucidates the complex interaction between primary tumors and the immune system that is mediated by exosomes and provides a foundation for the development of novel cancer immunotherapies that target ICAM1 with the aim of mitigating TNBC bone metastasis.Copyright © 2024 Elsevier Ltd. All rights reserved.