决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Empowering macrophages: the cancer fighters within the tumour microenvironment in mantle cell lymphoma.
Empowering macrophages: the cancer fighters within the tumour microenvironment in mantle cell lymphoma.
在套细胞淋巴瘤(MCL)中,肿瘤微环境(TME)内巨噬细胞的作用近期因其对预后和治疗反应的影响而受到关注。
近期,套细胞淋巴瘤(MCL)肿瘤微环境(TME)中的巨噬细胞受到关注,因为它们会影响预后和治疗应答。尽管巨噬细胞在MCL肿瘤组织中的绝对数量较少,近期研究仍发现其水平与预后相关,与其他淋巴瘤亚型中的趋势一致。以CD163等标志物识别的M2样巨噬细胞可促进血管生成并抑制免疫应答。MCL患者接受化学免疫治疗和靶向治疗的临床试验提示,M2样巨噬细胞水平升高会带来不良影响。来那度胺等免疫调节药物可降低MCL相关CD163⁺巨噬细胞水平,并增强巨噬细胞吞噬活性。类似地,靶向CD47“别吃我”信号并联合抗CD20抗体利妥昔单抗的临床策略,可增强巨噬细胞活性和对MCL肿瘤细胞的吞噬作用。嵌合抗原受体(CAR)T细胞等细胞疗法显示出前景,但仍面临多种挑战,因此CAR巨噬细胞(CAR-M)也逐渐引起关注。巨噬细胞被募集至TME后,具有吞噬功能,并能响应微环境变化;这提示,在复杂的MCL治疗中,当CAR-T疗法失效时,CAR-M可能成为一种可调控、可诱导的替代方案。
In Mantle Cell Lymphoma (MCL), the role of macrophages within the tumour microenvironment (TME) has recently gained attention due to their impact on prognosis and response to therapy. Despite their low absolute number in MCL tumour tissue, recent findings reveal an association between the levels of macrophages and prognosis, consistent with trends observed in other lymphoma subtypes. M2-like macrophages, identified by markers such as CD163, contribute to angiogenesis and suppression of the immune response. Clinical trials with MCL patients treated with chemoimmunotherapy and targeted treatments underscore the adverse impact of high levels of M2-like macrophages. Immunomodulatory drugs like lenalidomide reduce the levels of MCL-associated CD163 + macrophages and enhance macrophage phagocytic activity. Similarly, clinical approaches targeting the CD47 "don't eat me" signalling, in combination with the anti-CD20-antibody rituximab, demonstrate increased macrophage activity and phagocytosis of MCL tumour cells. Cell-based therapies such as chimeric antigen receptor (CAR) T-cell have shown promise but various challenges persist, leading to a potential interest in CAR-macrophages (CAR-M). When macrophages are recruited to the TME, they offer advantages including phagocytic function and responsiveness to microenvironment alterations, suggesting their potential as a manipulable and inducible alternative when CAR T-cell therapies fails in the complex landscape of MCL treatment.
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