通过靶向肿瘤相关巨噬细胞的嵌合受体工程化溶瘤病毒重振内源性抗肿瘤免疫
Rejuvenating endogenous antitumor immunity via a chimeric receptor-engineered oncolytic virus targeting tumor-associated macrophages.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Metabolic barriers to cancer immunotherapy.
Metabolic barriers to cancer immunotherapy.
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肿瘤微环境的几个非冗余特征促进了免疫抑制并限制了抗癌免疫反应。这些特征包括免疫浸润的物理屏障、抑制性免疫细胞的募集以及肿瘤细胞上配体的上调,这些配体与免疫细胞上的抑制性受体结合。近期对肿瘤微环境对抗肿瘤T细胞施加的代谢限制重要性的认识,已开始为免疫治疗抗癌策略提供信息。靶向代谢限制的治疗方法,如低葡萄糖水平、低pH、缺氧和抑制性代谢产物的生成,已显示出作为不同类型癌症联合疗法的前景。在本综述中,我们讨论了在免疫检查点阻断、过继细胞疗法和溶瘤病毒治疗背景下抗肿瘤T细胞反应的代谢方面,并讨论了新兴的联合策略。
Several non-redundant features of the tumour microenvironment facilitate immunosuppression and limit anticancer immune responses. These include physical barriers to immune infiltration, the recruitment of suppressive immune cells and the upregulation of ligands on tumour cells that bind to inhibitory receptors on immune cells. Recent insights into the importance of the metabolic restrictions imposed by the tumour microenvironment on antitumour T cells have begun to inform immunotherapeutic anticancer strategies.
Therapeutics that target metabolic restrictions, such as low glucose levels, a low pH, hypoxia and the generation of suppressive metabolites, have shown promise as combination therapies for different types of cancer. In this Review, we discuss the metabolic aspects of the antitumour T cell response in the context of immune checkpoint blockade, adoptive cell therapy and treatment with oncolytic viruses, and discuss emerging combination strategies.
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