工程化益生菌用于肿瘤靶向联合化学免疫治疗
Engineered probiotics for tumor-targeted combination chemoimmunotherapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:From blood draw to tumor infiltration: therapeutic variations in CAR-macrophage therapy for solid tumors.
From blood draw to tumor infiltration: therapeutic variations in CAR-macrophage therapy for solid tumors.
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工程化CAR-巨噬细胞(CAR-Ms)因其固有的抗肿瘤能力、吞噬作用以及在肿瘤微环境(TME)重塑中的免疫调节效应,已彻底改变了实体瘤免疫治疗。
通过使用包括PubMed、Google Scholar和Scopus在内的数据库进行了文献综述。数据提取基于1991年至2026年发表的相关文章,关键词包括嵌合抗原受体巨噬细胞、CAR-M、免疫治疗耐药、实体瘤和肿瘤微环境。涵盖领域:CAR-M来源于不同来源,但反过来在可扩展性、极化能力、表型转变、抗原逃逸和功能稳定性方面具有不同的优势和挑战。基因工程技术对于提高CAR-M疗效至关重要。除了内在工程化之外,将CAR-M与化疗、放疗、免疫检查点抑制剂以及纳米医学等新方法相结合,通过调节TME屏障和消除免疫逃逸机制来增强抗肿瘤效果。专家意见/评论:CAR-M疗法被认为是实体瘤有前景的下一代治疗方法,因为它具有克服淋巴细胞方法挑战的优势。然而,应考虑TME极化和患者反应的变异性,以实现最佳疗效。未来的进展应改进信号设计、整合新型免疫学方法、TME调节以及生物标志物指导的患者分层。目前有几种治疗实体瘤的方法,包括手术、化疗和放疗。然而,这些方法每种都有重要的局限性,例如对健康组织的损伤、治疗耐药或肿瘤复发。近年来,免疫疗法作为一种较新的策略出现,旨在增强人体自身免疫系统以识别和对抗癌细胞。尽管一些基于免疫的治疗已显示出令人鼓舞的结果,但许多疗法在治疗实体瘤时仍面临困难,因为免疫细胞往往无法有效进入肿瘤环境或在其中存活。巨噬细胞是一种天然会迁移至肿瘤内并清除有害或受损细胞的免疫细胞。因此,一种免疫治疗方法就是增强巨噬细胞。在这种方法中,患者的免疫细胞经过基因改造,使巨噬细胞能够更有效地识别并摧毁癌细胞。一旦进入肿瘤内部,这些细胞还能发出信号,吸引其他免疫细胞,并帮助将肿瘤环境转变为支持免疫攻击的环境。科学家还在测试通过将该疗法与化疗、放疗、免疫激活药物或纳米技术相结合来改进它的方法。尽管肿瘤耐药性和患者之间的差异等挑战仍然存在,但 CAR 巨噬细胞疗法代表了一种有前景的治疗难治性实体瘤的新策略。
INTRODUCTION: Engineering CAR-macrophages (CAR-Ms) has revolutionized the solid tumors immunotherapy, due to intrinsic anti-tumor capacity, phagocytosis ability, and immunomodulatory effects of macrophages in tumor microenvironment (TME) remodeling. METHODOLOGY: A literature review was conducted using databases including PubMed, Google Scholar, and Scopus. The data was extracted using relevant articles published from 1991 to 2026 based on key words such as Chimeric Antigen Receptor Macrophages, CAR-M, Immunotherapy Resistance, Solid Tumors, and Tumor Microenvironment.
AREAS COVERED: CAR-Ms originate from different sources, but in turn come with distinct advantages and challenges regarding scalability, polarization capacity, phenotype shift, antigen escape, and functional stability. Genetic engineering techniques are essential to increase CAR-M efficacy.
Along with intrinsic engineering, the integration of CAR-Ms with chemotherapy, radiotherapy, immune checkpoint inhibitors, and new methods, such as nanomedicine, enhances antitumor effects by modulating TME barriers and abrogation of immune evasion mechanisms. EXPERT OPINION/COMMENTARY: CAR-m therapy is represented as a promising next-generation treatment for solid tumors, due to its strength to overcome the challenges of lymphocyte approaches.
However, TME polarization and variability in patient response should be considered to achieve optimal efficacy. Future advancements should improve signaling design, integration of novel immunologic methods, TME modulation, and biomarker-guided patient stratification. Several treatments are currently available for solid tumors, including surgery, chemotherapy, and radiotherapy.
However, each of these approaches has important limitations, such as damage to healthy tissues, treatment resistance, or tumor recurrence. In recent years, immunotherapy has emerged as a newer strategy that aims to strengthen the body’s own immune system to recognize and fight cancer cells.
Although some immune-based treatments have shown promising results, many still face difficulties in treating solid tumors because immune cells often cannot effectively enter or survive within the tumor environment. Macrophages are immune cells that naturally move into tumors and remove harmful or damaged cells.
Therefore, one method of immunotherapy is to enhance macrophages. In this approach, a patient’s immune cells are genetically modified so that macrophages can recognize and destroy cancer cells more efficiently. Once inside the tumor, these cells can also send signals that attract other immune cells and help turn the tumor environment into one that supports an immune attack.
Scientists are also testing ways to improve this therapy by combining it with chemotherapy, radiation, immune-activating drugs, or nanotechnology. Although challenges such as tumor resistance and differences between patients still remain, CAR macrophage therapy represents a promising new strategy for treating difficult solid tumors.
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