Harnessing the tumor microenvironment to boost adoptive T cell therapy with engineered lymphocytes for solid tumors.

IF 7.9 2区 医学 Q1 IMMUNOLOGY Seminars in Immunopathology Pub Date : 2024-07-25 DOI:10.1007/s00281-024-01011-y
Martina Spiga, Elisa Martini, Maria Chiara Maffia, Fabio Ciceri, Eliana Ruggiero, Alessia Potenza, Chiara Bonini
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Abstract

Adoptive cell therapy (ACT) using Chimeric Antigen Receptor (CAR) and T Cell Receptor (TCR) engineered T cells represents an innovative therapeutic approach for the treatment of hematological malignancies, yet its application for solid tumors is still suboptimal. The tumor microenvironment (TME) places several challenges to overcome for a satisfactory therapeutic effect, such as physical barriers (fibrotic capsule and stroma), and inhibitory signals impeding T cell function. Some of these obstacles can be faced by combining ACT with other anti-tumor approaches, such as chemo/radiotherapy and checkpoint inhibitors. On the other hand, cutting edge technological tools offer the opportunity to overcome and, in some cases, take advantage of TME intrinsic characteristics to boost ACT efficacy. These include: the exploitation of chemokine gradients and integrin expression for preferential T-cell homing and extravasation; metabolic changes that have direct or indirect effects on TCR-T and CAR-T cells by increasing antigen presentation and reshaping T cell phenotype; introduction of additional synthetic receptors on TCR-T and CAR-T cells with the aim of increasing T cells survival and fitness.

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利用肿瘤微环境,用工程淋巴细胞促进实体瘤的采纳 T 细胞疗法。
使用嵌合抗原受体(CAR)和T细胞受体(TCR)工程T细胞的适应性细胞疗法(ACT)是治疗血液恶性肿瘤的一种创新治疗方法,但其在实体瘤中的应用仍不理想。肿瘤微环境(TME)是取得满意疗效需要克服的几个挑战,如物理障碍(纤维囊和基质)和阻碍 T 细胞功能的抑制信号。通过将 ACT 与化疗/放疗和检查点抑制剂等其他抗肿瘤方法相结合,可以克服其中的一些障碍。另一方面,尖端技术工具为克服这些障碍提供了机会,在某些情况下,还能利用 TME 的固有特性提高 ACT 的疗效。这些特征包括:利用趋化因子梯度和整合素表达来实现 T 细胞的优先归巢和外渗;通过增加抗原呈递和重塑 T 细胞表型,对 TCR-T 和 CAR-T 细胞产生直接或间接影响的新陈代谢变化;在 TCR-T 和 CAR-T 细胞上引入额外的合成受体,以提高 T 细胞的存活率和活力。
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来源期刊
Seminars in Immunopathology
Seminars in Immunopathology 医学-病理学
CiteScore
19.80
自引率
2.20%
发文量
69
审稿时长
12 months
期刊介绍: The aim of Seminars in Immunopathology is to bring clinicians and pathologists up-to-date on developments in the field of immunopathology.For this purpose topical issues will be organized usually with the help of a guest editor.Recent developments are summarized in review articles by authors who have personally contributed to the specific topic.
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