基于 DNA 超分子水凝胶的保护性 NK 细胞储库用于增强三阴性乳腺癌治疗
Protective NK Cell Reservoir Based on DNA Supramolecular Hydrogel for Enhanced Triple-Negative Breast Cancer Therapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Tumor-infiltrating lymphocytes in triple-negative breast cancer: molecular mechanisms, spatial regulation, and therapeutic implications.
Tumor-infiltrating lymphocytes in triple-negative breast cancer: molecular mechanisms, spatial regulation, and therapeutic implications.
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三阴性乳腺癌(TNBC)因其侵袭性强且治疗选择有限,构成了重大的治疗挑战。本综述综合了近年来在理解TNBC肿瘤免疫微环境(TIME)方面的进展,超越了简单的“冷”肿瘤范式,将其描绘为一个复杂的、整合的生态系统。
我们详细阐述了多层网络,包括动态代谢交互、转录重编程、癌症相关成纤维细胞(CAFs)异质性以及空间结构,如何共同塑造抗肿瘤免疫并决定TIL(肿瘤浸润淋巴细胞)(TILs)的疗效。尽管已取得显著进展,我们仍批判性地审视了尚存的巨大转化差距,因为许多见解仍源自临床前模型。
我们认为,合理设计的联合方案,包括对已获批临床药物的重定位利用,提供了一条近期可行的务实路径。此外,我们探讨了从纯粹抑制性策略向选择性过度激活免疫或代谢通路的概念转变,以此作为应对当前治疗挑战的手段。
最后,我们强调,整合高维数据,包括CAF分类、免疫表型分析和空间映射,对于开发真正的精准免疫治疗至关重要。本综述得出结论,这些方法的融合正在为下一代个体化TNBC治疗构建一个更全面且可操作的框架。
Triple-negative breast cancer (TNBC) represents a profound therapeutic challenge due to its aggressive nature and limited treatment options. This review synthesizes recent advances in understanding the TNBC tumor immune microenvironment (TIME), moving beyond the simplistic “cold” tumor paradigm to depict it as a complex, integrated ecosystem.
We detail how multilayered networks, including dynamic metabolic cross-talk, transcriptional reprogramming, cancer-associated fibroblasts (CAFs) heterogeneity, and spatial architecture, collectively shape antitumor immunity and determine the efficacy of tumor-infiltrating lymphocytes (TILs). While significant progress has been made, we critically examine the substantial translational gaps that remain, as many insights are still derived from preclinical models.
We argue that rationally designed combinations, including the repurposing of clinically approved drugs, offer a near-term pragmatic pathway.
Furthermore, we explore the conceptual shift from purely inhibitory strategies toward the selective overactivation of immune or metabolic pathways as a means to address current therapeutic challenges.
Finally, we emphasize that the integration of high-dimensional data, including CAF taxonomy, immune phenotyping, and spatial mapping, is pivotal for the development of truly precision immunotherapies. This review concludes that the convergence of these approaches is forging a more comprehensive and actionable framework for the next generation of patient-tailored TNBC treatments.
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