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:The Landscape and Clinical Application of the Tumor Microenvironment in Gastroenteropancreatic Neuroendocrine Neoplasms.
The Landscape and Clinical Application of the Tumor Microenvironment in Gastroenteropancreatic Neuroendocrine Neoplasms.
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胃肠胰神经内分泌肿瘤具有高度异质性。神经内分泌肿瘤细胞与肿瘤微环境密切相关。肿瘤浸润免疫细胞之间以及免疫细胞与肿瘤细胞之间相互教育。免疫细胞具有促肿瘤和抗肿瘤的双重作用。免疫环境有利于肿瘤的侵袭和转移;反过来,肿瘤细胞可以改变免疫环境。这些细胞还形成细胞因子、免疫检查点系统和三级淋巴结构,参与相互适应的过程。此外,成纤维细胞、血管结构和微生物群与肿瘤细胞表现出相互作用。从基础到临床,与肿瘤微环境相关的临床实践也被认为具有前景。靶向免疫成分和血管生成调节分子已被证明是有效的。免疫检查点抑制剂、过继细胞疗法和溶瘤病毒的临床疗效仍有待临床试验进一步讨论。此外,联合治疗对于晚期高级别肿瘤是可行的。基于多组学结果对肿瘤微环境的调控可以提示创新性治疗策略,以防止肿瘤成功实现免疫逃逸并支持抗肿瘤效应。
Gastroenteropancreatic neuroendocrine neoplasms feature high heterogeneity. Neuroendocrine tumor cells are closely associated with the tumor microenvironment. Tumor-infiltrating immune cells are mutually educated by each other and by tumor cells. Immune cells have dual protumorigenic and antitumorigenic effects.
The immune environment is conducive to the invasion and metastasis of the tumor; in turn, tumor cells can change the immune environment. These cells also form cytokines, immune checkpoint systems, and tertiary lymphoid structures to participate in the process of mutual adaptation.
Additionally, the fibroblasts, vascular structure, and microbiota exhibit interactions with tumor cells. From bench to bedside, clinical practice related to the tumor microenvironment is also regarded as promising. Targeting immune components and angiogenic regulatory molecules has been shown to be effective. The clinical efficacy of immune checkpoint inhibitors, adoptive cell therapy, and oncolytic viruses remains to be further discussed in clinical trials.
Moreover, combination therapy is feasible for advanced high-grade tumors. The regulation of the tumor microenvironment based on multiple omics results can suggest innovative therapeutic strategies to prevent tumors from succeeding in immune escape and to support antitumoral effects.
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