Frontiers in immunology · 2026
CX3CR1 identifies a potent effector CD8+ T cell subset associated with anti-PD-1 therapeutic efficacy in colorectal cancer.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Ma Jiajin, Wu Yue, Chen Rongzhang, Wang Nuo, Liu Yirui, Chen Lujun, Wu Shaoxian, Zheng Xiao
Аннотация
BACKGROUND: The therapeutic landscape for deficient mismatch repair (dMMR) colorectal cancer (CRC) has been fundamentally transformed by the introduction of immune checkpoint inhibitors (ICIs). Yet, a significant fraction of patients exhibits primary or acquired resistance, underscoring a critical unmet need to decode the heterogeneity of tumor-infiltrating CD8+T cells. Identifying the effector subsets that truly drive tumor control will be essential for refining patient stratification and optimizing therapeutic interventions.
METHODS: By leveraging a multi-dimensional approach that combined single-cell RNA sequencing (scRNA-seq), multiplex immunohistochemistry (mIHC), extensive clinical data mining, and in vivo murine models, we comprehensively delineated the phenotypic profile, regulatory networks, and clinical relevance of intratumoral CX3CR1+CD8+T cells.
RESULTS: We uncovered a unique CX3CR1+CD8+ T cell subset exhibiting a Temra-like terminal effector phenotype characterized by potent cytotoxicity (GNLY, PRF1) and low exhaustion. Clinically, enrichment of this population emerged as a strong, independent predictor of improved overall survival in CRC. Mechanistically, effective anti-PD-1 therapy revitalizes anti-tumor immunity by specifically promoting the proliferation and maintaining the function of these CX3CR1+ effector cells within the tumor. SCENIC analysis further revealed that this differentiation pathway is orchestrated by ETS1, PRDM1 and STAT1 driven regulatory network, which is markedly induced following PD-1 inhibition to enhance metabolic fitness and cellular recruitment.
CONCLUSION: This study characterizes CX3CR1+CD8+T cells as a key effector subset predicting prognosis and immunotherapy response in colorectal cancer. These insights not only support their use as a clinically meaningful biomarker but also highlight the regulatory network orchestrated by ETS1 and PRDM1 as a promising avenue for overcoming immune resistance.
METHODS: By leveraging a multi-dimensional approach that combined single-cell RNA sequencing (scRNA-seq), multiplex immunohistochemistry (mIHC), extensive clinical data mining, and in vivo murine models, we comprehensively delineated the phenotypic profile, regulatory networks, and clinical relevance of intratumoral CX3CR1+CD8+T cells.
RESULTS: We uncovered a unique CX3CR1+CD8+ T cell subset exhibiting a Temra-like terminal effector phenotype characterized by potent cytotoxicity (GNLY, PRF1) and low exhaustion. Clinically, enrichment of this population emerged as a strong, independent predictor of improved overall survival in CRC. Mechanistically, effective anti-PD-1 therapy revitalizes anti-tumor immunity by specifically promoting the proliferation and maintaining the function of these CX3CR1+ effector cells within the tumor. SCENIC analysis further revealed that this differentiation pathway is orchestrated by ETS1, PRDM1 and STAT1 driven regulatory network, which is markedly induced following PD-1 inhibition to enhance metabolic fitness and cellular recruitment.
CONCLUSION: This study characterizes CX3CR1+CD8+T cells as a key effector subset predicting prognosis and immunotherapy response in colorectal cancer. These insights not only support their use as a clinically meaningful biomarker but also highlight the regulatory network orchestrated by ETS1 and PRDM1 as a promising avenue for overcoming immune resistance.