肿瘤细胞治疗研究
英文原题：Immune cell-derived exosomes in cancer: double-edged mechanisms of antitumor immunity and tumor progression.
免疫细胞来源的外泌体是肿瘤微环境中细胞间通讯的重要介质。
免疫细胞来源的外泌体是肿瘤微环境中细胞间通讯的重要介质。其生物学效应受免疫细胞来源和活化状态、囊泡货物、受体细胞类型以及肿瘤背景的影响。本综述探讨免疫细胞来源的外泌体作为癌症相关信号的双向调控因子，重点阐述其抗肿瘤和促肿瘤机制，而非仅按亲本细胞类型进行分类。抗肿瘤外泌体可增强抗原呈递、激活NK 细胞和T细胞应答、重编程肿瘤相关巨噬细胞、降低免疫检查点信号、诱导肿瘤细胞死亡，并抑制肿瘤生长和转移。相反，调节性T细胞（Tregs）、髓源性抑制细胞（MDSCs）、肿瘤相关巨噬细胞（TAMs）及其他免疫群体释放的外泌体可能促进免疫抑制、耐受性重编程、检查点介导的免疫逃逸、侵袭、转移和治疗耐药。这些效应通过转移蛋白质、受体、酶、细胞因子相关分子、microRNAs、长非编码RNAs及其他调控货物来介导，从而调节NF-κB、MAPK/ERK、PI3K-AKT-mTOR、STAT3、PD-1/PD-L1、凋亡及β-catenin/HIF-1α相关通路等信号网络。尽管具有治疗和诊断潜力，其临床转化仍受限于细胞外囊泡异质性、功能性货物鉴定不完整、分离和表征方法不一致、生产制造挑战、储存不稳定性以及在体内追踪囊泡的困难。未来的研究应致力于明确亲本细胞状态、外泌体货物、受体细胞身份以及下游生物学反应之间的关系。此外，将实验数据与计算和基于人工智能的方法相结合，可能有助于实现单囊泡分类、推断EV细胞来源，以及开发更具可重复性的基于外泌体的癌症疗法。
Immune cell-derived exosomes are important mediators of intercellular communication within the tumor microenvironment. Their biological effects are influenced by the immune-cell source and activation state, vesicular cargo, recipient-cell type, and tumor context. This review examines immune cell-derived exosomes as bidirectional regulators of cancer-associated signaling, with emphasis on their antitumor and protumor mechanisms rather than classification by parent cell type alone. Antitumor exosomes can enhance antigen presentation, activate natural killer cell and T-cell responses, reprogram tumor-associated macrophages, reduce immune-checkpoint signaling, induce tumor-cell death, and suppress tumor growth and metastasis. Conversely, exosomes released by regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and other immune populations may promote immune suppression, tolerogenic reprogramming, checkpoint-mediated immune escape, invasion, metastasis, and treatment resistance. These effects are mediated through the transfer of proteins, receptors, enzymes, cytokine-related molecules, microRNAs, long non-coding RNAs, and other regulatory cargo that modulate signaling networks such as NF-κB, MAPK/ERK, PI3K-AKT-mTOR, STAT3, PD-1/PD-L1, apoptotic, and β-catenin/HIF-1α-associated pathways. Despite their therapeutic and diagnostic potential, clinical translation remains limited by extracellular-vesicle heterogeneity, incomplete identification of functional cargo, inconsistent isolation and characterization methods, manufacturing challenges, storage instability, and difficulties in tracking vesicles in vivo . Future studies should aim to define the relationships among parent-cell state, exosomal cargo, recipient-cell identity, and downstream biological responses. Additionally, integrating experimental data with computational and artificial-intelligence-based approaches may support single-vesicle classification, inference of EV cellular origin, and the development of more reproducible exosome-based cancer therapies.
MEMBER ACCOUNT
登录成功会直接打开下一页。
