CX3CR1+CD8+ T cells: Key players in antitumor immunity

• Published in: Cancer science 2024-12, Vol.115 (12), p.3838-3845
• Main Authors: Ma, Jiajin, Wu, Yue, Wu, Shaoxian, Fang, Zhang, Chen, Lujun, Jiang, Jingting, Zheng, Xiao
• Format: Article
• Language: English
• Subjects: Animals; Cancer; CD8 antigen; CD8+ T cell; CD8-Positive T-Lymphocytes - immunology; Cell interactions; Cells; Chemokine CX3CL1 - immunology; Chemokine CX3CL1 - metabolism; Chemokines; CX3C Chemokine Receptor 1 - metabolism; CX3CR1; CX3CR1 protein; Cytokines; Cytotoxicity; Development and progression; Humans; Immune system; Immunotherapy; Immunotherapy - methods; Leukocytes; Ligands; Lymphocytes; Lymphocytes T; Neoplasms - immunology; Neoplasms - therapy; Proteins; Review; Signal Transduction - immunology; T cells; Tumor microenvironment; Tumor Microenvironment - immunology; Tumor necrosis factor-TNF; Tumors
• ISSN: 1347-9032; 1349-7006; 1349-7006
• DOI: 10.1111/cas.16359

CX3CR1 functions as the specific receptor for the chemokine CX3CL1, demonstrating expression across a broad spectrum of immune cells. This underscores its pivotal role in communication and response mechanisms within the immune system. Upon engagement with CX3CL1, CX3CR1 initiates a cascade of downstream signaling pathways that regulate various biological functions. In the context of tumor progression, the intricate and inhibitory nature of the tumor microenvironment presents a significant challenge to current clinical treatment techniques. This review aims to comprehensively explore the tumor‐destructive potential shown by CX3CR1+CD8+ T cells. Simultaneously, it investigates the promising prospects of utilizing CX3CR1 in future tumor immunotherapies. This article provides a comprehensive review of recent research advancements in the field of tumor immunology, focusing particularly on a unique subset of CX3CR1+CD8+ T cells and their distinct advantages. These cells show immense potential in tumor immunotherapy, especially within the realm of cellular immunotherapy, due to their ability to migrate toward tumors, exert cytotoxic effects, selectively recognize tumor cells, and exhibit minimal expression of co‐inhibitory molecules. Concurrently, the effectiveness of chimeric antigen receptor T (CAR‐T) cells expressing high levels of CX3CR1 in the clinical management of solid tumors requires further validation through future phase I and II clinical trials. Indeed, as research advances, these pioneering approaches are poised to offer new avenues of hope for countless cancer patients.