免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
异源抗原组装的纳米疫苗增强 TILs 的多功能性以对抗肿瘤生长和转移
英文原题：Heteroantigen-assembled nanovaccine enhances the polyfunctionality of TILs against tumor growth and metastasis.
查看英文原题
Heteroantigen-assembled nanovaccine enhances the polyfunctionality of TILs against tumor growth and metastasis.
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中文摘要
TIL（肿瘤浸润淋巴细胞）（TILs）的功能障碍与肿瘤生长和转移失控直接相关。迫切需要新的方法和深刻的见解来挽救TILs功能障碍。在此，我们基于肿瘤的MHC-I表位和MHC-II表位设计了两种异源抗原，并通过静电相互作用和π-π堆积将异源抗原组装成异源抗原组装纳米疫苗（HANV）。HANV不仅在体内显著增加了CD8+和CD4+ TILs的丰度，还引发了更强的CD8+和CD4+ TILs多功能性。CD8+和CD4+ TILs增强的多功能性正相关于黑色素瘤小鼠模型中肿瘤生长和转移的抑制。我们还验证了含核苷酸结合寡聚化结构域蛋白2（NOD2）以时间性免疫调节方式主导增强TILs的抗肿瘤能力。这项工作为开发HANV作为塑造TILs多功能性以应对肿瘤生长和转移的合理策略提供了新见解。
展开英文摘要原文
The dysfunction of tumor infiltrating lymphocytes (TILs) directly correlates with out of control of tumor growth and metastasis. New approaches and insightful clarity for rescuing TILs dysfunction are urgently needed.
Here, we design two heterogenous antigens based on MHC-I epitope and MHC-II epitope from tumor, and assemble heterogenous antigens by electrostatic interactions and - stacking into heteroantigen-assembled nanovaccine (HANV). HANV not only significantly increases the abundance of CD8 + and CD4 + TILs, but also elicits stronger polyfunctionality of CD8 + and CD4 + TILs in vivo. Enhanced polyfunctionality of CD8 + and CD4 + TILs positively correlate to suppression of tumor growth and metastasis in melanoma-bearing mouse models.
We also validate that nucleotide-binding oligomerization domain-containing protein 2 (NOD2) dominantly enhances anti-tumor capacity of TILs in a temporal immunoregulation manner. This work presents a new insight in developing HANV as a rational strategy to shape TILs polyfunctionality for tumor growth and metastasis.
论文信息
- 作者
- Wei L、Zhang Y、Wang R、Liu S、Luo J、Ma Y、Wang H、Liu Y
- 第一作者单位
- Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College; Kunming, Yunnan, 650000, China; State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Hospital, Nanjing Medical University; Nanjing 211166, China; Department of Immunology, Key Laboratory of Immunological Environment and Disease, Key Laboratory of Human Functional Genomics of Jiangsu Province, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Gusu School, Nanjing Medical University; Nanjing 211166, China; Department of Epidemiology, National Vaccine Innovation Platform, Center for Global Health, Nanjing Medical University, Nanjing, China; Department of Central Laboratory, The Affiliated Huai'an N0.1 People's Hospital, Nanjing Medical University, Huai'an, 223300, China.China
- 通讯作者单位
- State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Hospital, Nanjing Medical University; Nanjing 211166, China; Department of Immunology, Key Laboratory of Immunological Environment and Disease, Key Laboratory of Human Functional Genomics of Jiangsu Province, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Gusu School, Nanjing Medical University; Nanjing 211166, China; Department of Epidemiology, National Vaccine Innovation Platform, Center for Global Health, Nanjing Medical University, Nanjing, China; Department of Central Laboratory, The Affiliated Huai'an N0.1 People's Hospital, Nanjing Medical University, Huai'an, 223300, China. Electronic address: chenyun@njmu.edu.cn.China
- 文献类型
- 非美国政府资助研究
- 期刊
- Biomaterials2023 Nov
- 原文标识
- PubMed 37666102 · DOI 10.1016/j.biomaterials.2023.122297