Zhang Xiaolan, Liu Lingbo
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Int J Mol Sci. 2024 Nov 22;25(23):12550. doi: 10.3390/ijms252312550.
Malignant tumors can evade immune surveillance and elimination through multiple mechanisms, with the induction of immune cell dysfunction serving as a crucial strategy. Mounting evidence indicates that T cell senescence constitutes the primary mechanism underlying T cell dysfunction in acute myeloid leukemia (AML) and represents one of the potential causes of immunotherapy failure. AML usually progresses rapidly and is highly susceptible to drug resistance, thereby resulting in recurrence and patient mortality. Hence, disrupting the immune interface within the bone marrow microenvironment of AML has emerged as a critical objective for synergistically enhancing tumor immunotherapy. In this review, we summarize the general characteristics, distinctive phenotypes, and regulatory signaling networks of senescent T cells and highlight their potential clinical significance in the bone marrow microenvironment of AML. Additionally, we discuss potential therapeutic strategies for alleviating and reversing T cell senescence.
恶性肿瘤可通过多种机制逃避免疫监视和清除，诱导免疫细胞功能障碍是一种关键策略。越来越多的证据表明，T细胞衰老构成急性髓系白血病（AML）中T细胞功能障碍的主要机制，也是免疫治疗失败的潜在原因之一。AML通常进展迅速，且极易产生耐药性，从而导致复发和患者死亡。因此，破坏AML骨髓微环境中的免疫界面已成为协同增强肿瘤免疫治疗的关键目标。在这篇综述中，我们总结了衰老T细胞的一般特征、独特表型和调控信号网络，并强调了它们在AML骨髓微环境中的潜在临床意义。此外，我们还讨论了减轻和逆转T细胞衰老的潜在治疗策略。
