通过淋巴结靶向化免疫化疗诱导干细胞样 CD8 T 细胞反应可引发全身性肿瘤控制。
Elicitation of stem-like CD8 T cell responses via lymph node-targeted chemoimmunotherapy evokes systemic tumor control.
机构信息
Parker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA.
School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.
出版信息
J Immunother Cancer. 2022 Sep;10(9). doi: 10.1136/jitc-2022-005079.
BACKGROUND
Tumor-draining lymph nodes (TdLNs) are critical in the regulation of local and systemic antitumor T cell immunity and are implicated in coordinating responses to immunomodulatory therapies.
METHODS
Biomaterial nanoparticles that deliver chemotherapeutic drug paclitaxel to TdLNs were leveraged to explore its effects in combination and immune checkpoint blockade (ICB) antibody immunotherapy to determine the benefit of TdLN-directed chemoimmunotherapy on tumor control.
RESULTS
Accumulation of immunotherapeutic drugs in combination within TdLNs synergistically enhanced systemic T cell responses that led to improved control of local and disseminated disease and enhanced survival in multiple murine breast tumor models.
CONCLUSIONS
These findings suggest a previously underappreciated role of secondary lymphoid tissues in mediating effects of chemoimmunotherapy and demonstrate the potential for nanotechnology to unleashing drug synergies via lymph node targeted delivery to elicit improved response of breast and other cancers.
背景
肿瘤引流淋巴结（TdLNs）在调节局部和全身抗肿瘤 T 细胞免疫方面至关重要，并与协调免疫调节治疗的反应有关。
方法
利用将化疗药物紫杉醇递送至 TdLNs 的生物材料纳米颗粒，探索其与免疫检查点阻断（ICB）抗体免疫疗法联合使用的效果，以确定 TdLN 导向化疗免疫疗法对肿瘤控制的益处。
结果
在 TdLNs 中联合使用免疫治疗药物会协同增强全身 T 细胞反应，从而改善局部和播散性疾病的控制，并提高多种小鼠乳腺癌模型的存活率。
结论
这些发现表明次级淋巴组织在介导化疗免疫治疗效果方面具有先前未被充分认识的作用，并证明了纳米技术通过淋巴结靶向递送来释放药物协同作用的潜力，从而改善乳腺癌和其他癌症的反应。
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