CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:T cell exhaustion in pediatric B-ALL: current knowledge and future perspectives.
T cell exhaustion in pediatric B-ALL: current knowledge and future perspectives.
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B细胞急性淋巴细胞白血病(B-ALL)是儿童最常见的恶性肿瘤,每年占北美儿童新发癌症诊断的20-25%。该白血病通常经过3-5年的潜伏期后,起源于子宫内产生的前白血病B细胞前体群体。尽管B-ALL细胞的免疫原性普遍较低,但新出现的证据表明,T细胞耗竭——一种以抑制性受体持续表达和功能逐渐衰退为特征的状态——是疾病进展的一个促成因素。在诊断时及治疗期间,B-ALL患儿T细胞上常检测到抑制性受体的表达。鉴于T细胞耗竭是增强保护性免疫活性的一个可干预靶点,本综述总结了临床和临床前环境中关于儿童B-ALL进展过程中T细胞耗竭的证据,并讨论了将免疫检查点阻断纳入儿童B-ALL治疗方案中的机遇与挑战。
B-cell acute lymphoblastic leukemia (B-ALL) is the most common pediatric malignancy, accounting for 20-25% of all new cancer diagnoses in North American children each year. The leukemia arises, most commonly after a latency of 3-5 years, from a preleukemic B cell precursor population generated in utero . Despite the generally low immunogenicity of B-ALL cells, emerging evidence implicates T cell exhaustion - a state marked by sustained expression of inhibitory receptors and progressive functional decline - as a contributor to disease progression.
Expression of inhibitory receptors is frequently detected on T cells from children with B-ALL at diagnosis and during therapy. As T cell exhaustion presents an actionable target for enhancing protective immune activity, in this review we summarize evidence from both clinical and pre-clinical settings for T cell exhaustion during pediatric B-ALL progression and discuss the opportunities and challenges to incorporating immune checkpoint blockade into pediatric B-ALL therapy regimens.
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