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Immunotherapeutic modulation of the suppressive liver and tumor microenvironments.

机译:抑制性肝脏和肿瘤微环境的免疫治疗调节。

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摘要

The liver is an immunologically unique organ, consisting of resident hematopoietic and parenchymal cells which often contribute to a relatively tolerant microenvironment. It is also becoming increasingly clear that tumor-induced immunosuppression occurs via many of the same cellular mechanisms which contribute to the tolerogenic liver microenvironment. Myeloid cells, consisting of dendritic cells (DC), macrophages and myeloid derived suppressor cells (MDSC), have been implicated in providing a tolerogenic liver environment and immune dysfunction within the tumor microenvironment which can favor tumor progression. As we increase our understanding of the biological mechanisms involved for each phenotypic and/or functionally distinct leukocyte subset, immunotherapeutic strategies can be developed to overcome the inherent barriers to the development of improved strategies for the treatment of liver disease and tumors. In this review, we discuss the principal myeloid cell-based contributions to immunosuppression that are shared between the liver and tumor microenvironments. We further highlight immune-based strategies shown to modulate immunoregulatory cells within each microenvironment and enhance anti-tumor responses.
机译:肝脏是一种免疫学上独特的器官,由常驻造血细胞和实质细胞组成,这些细胞通常有助于形成相对耐受的微环境。越来越明显的是,肿瘤诱导的免疫抑制是通过许多相同的细胞机制发生的,这些机制对致耐受性肝微环境有贡献。由树突状细胞(DC),巨噬细胞和髓样来源的抑制细胞(MDSC)组成的髓样细胞已牵涉在肿瘤微环境中提供可耐受的肝环境和免疫功能障碍,从而有利于肿瘤进展。随着我们对涉及每个表型和/或功能独特的白细胞亚群的生物学机制的了解加深,可以制定免疫治疗策略来克服固有的障碍,从而阻碍了开发改进的肝病和肿瘤治疗策略的发展。在这篇综述中,我们讨论了肝脏和肿瘤微环境之间共享的主要基于髓细胞的免疫抑制作用。我们进一步强调基于免疫的策略,可以调节每个微环境中的免疫调节细胞并增强抗肿瘤反应。

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