了解B细胞恶性肿瘤中的免疫-基质微环境以实现有效的免疫治疗。

Understanding the Immune-Stroma Microenvironment in B Cell Malignancies for Effective Immunotherapy.

作者信息

Apollonio Benedetta, Ioannou Nikolaos, Papazoglou Despoina, Ramsay Alan G

机构信息

Faculty of Life Sciences & Medicine, School of Cancer and Pharmaceutical Sciences, King's College London, London, United Kingdom.

出版信息

Front Oncol. 2021 Mar 25;11:626818. doi: 10.3389/fonc.2021.626818. eCollection 2021.

Abstract

Cancers, including lymphomas, develop in complex tissue environments where malignant cells actively promote the creation of a pro-tumoral niche that suppresses effective anti-tumor effector T cell responses. Research is revealing that the tumor microenvironment (TME) differs between different types of lymphoma, covering inflamed environments, as exemplified by Hodgkin lymphoma, to non-inflamed TMEs as seen in chronic lymphocytic leukemia (CLL) or diffuse-large B-cell lymphoma (DLBCL). In this review we consider how T cells and interferon-driven inflammatory signaling contribute to the regulation of anti-tumor immune responses, as well as sensitivity to anti-PD-1 immune checkpoint blockade immunotherapy. We discuss tumor intrinsic and extrinsic mechanisms critical to anti-tumor immune responses, as well as sensitivity to immunotherapies, before adding an additional layer of complexity within the TME: the immunoregulatory role of non-hematopoietic stromal cells that co-evolve with tumors. Studying the intricate interactions between the immune-stroma lymphoma TME should help to design next-generation immunotherapies and combination treatment strategies to overcome complex TME-driven immune suppression.

摘要

癌症,包括淋巴瘤,在复杂的组织环境中发生,其中恶性细胞积极促进促肿瘤微环境的形成,这种微环境会抑制有效的抗肿瘤效应T细胞反应。研究表明,不同类型淋巴瘤的肿瘤微环境(TME)有所不同,从霍奇金淋巴瘤所代表的炎症环境到慢性淋巴细胞白血病(CLL)或弥漫性大B细胞淋巴瘤(DLBCL)中所见的非炎症性TME。在本综述中,我们探讨T细胞和干扰素驱动的炎症信号如何促进抗肿瘤免疫反应的调节,以及对抗程序性死亡蛋白1(PD-1)免疫检查点阻断免疫疗法的敏感性。在增加TME内另一层复杂性之前,我们讨论对抗肿瘤免疫反应以及对免疫疗法敏感性至关重要的肿瘤内在和外在机制:与肿瘤共同进化的非造血基质细胞的免疫调节作用。研究免疫-基质-淋巴瘤TME之间的复杂相互作用应有助于设计下一代免疫疗法和联合治疗策略,以克服复杂的TME驱动的免疫抑制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a981/8027510/945a66aac40a/fonc-11-626818-g001.jpg

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