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用传统1型树突状细胞进行免疫治疗可诱导免疫记忆并限制肿瘤复发。

Immunotherapy with conventional type-1 dendritic cells induces immune memory and limits tumor relapse.

作者信息

Heras-Murillo Ignacio, Mañanes Diego, Munné Pablo, Núñez Vanessa, Herrera Jessica, Catalá-Montoro Mauro, Alvarez Maite, Del Pozo Miguel A, Melero Ignacio, Wculek Stefanie K, Sancho David

机构信息

Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.

Universidad Autónoma de Madrid, Escuela de Doctorado, Madrid, Spain.

出版信息

Nat Commun. 2025 Apr 9;16(1):3369. doi: 10.1038/s41467-025-58289-1.


DOI:10.1038/s41467-025-58289-1
PMID:40204706
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11982544/
Abstract

The potential of dendritic cell (DC) vaccination against cancer is not fully achieved. Little is known about the precise nature of the anti-cancer immune response triggered by different natural DC subsets and their relevance in preventing postsurgical tumor recurrence. Here, we use mouse splenic conventional DC1s (cDC1s) or cDC2s pulsed with tumor cell lysates to generate DC vaccines. cDC1-based vaccination induces a stronger effector and memory CD4 and CD8 anti-tumor T cell response, leading to a better control of tumors treated either therapeutically or prophylactically. Using an experimental model of tumor relapse, we show that adjuvant or neoadjuvant cDC1 vaccination improves anti-tumor immune memory, particularly by increasing the infiltrates of CD4 tissue resident memory (Trm) and CD8 memory T cells. This translates into complete prevention of tumor relapses. Moreover, elevated abundance of cDC1s positively correlates with CD4 Trm presence, and both associate with enhanced survival in human breast cancer and melanoma. Our findings suggest that cDC1-based vaccination excels at immune memory induction and prevention of cancer recurrence.

摘要

树突状细胞(DC)癌症疫苗的潜力尚未得到充分发挥。对于不同天然DC亚群引发的抗癌免疫反应的确切性质及其在预防术后肿瘤复发中的相关性,我们了解甚少。在此,我们使用用肿瘤细胞裂解物脉冲处理的小鼠脾脏常规DC1(cDC1)或cDC2来制备DC疫苗。基于cDC1的疫苗接种可诱导更强的效应和记忆性CD4和CD8抗肿瘤T细胞反应,从而更好地控制接受治疗性或预防性治疗的肿瘤。使用肿瘤复发的实验模型,我们发现辅助性或新辅助性cDC1疫苗接种可改善抗肿瘤免疫记忆,特别是通过增加CD4组织驻留记忆(Trm)和CD8记忆T细胞的浸润。这转化为对肿瘤复发的完全预防。此外,cDC1s丰度的升高与CD4 Trm的存在呈正相关,且二者均与人类乳腺癌和黑色素瘤患者的生存率提高相关。我们的研究结果表明,基于cDC1的疫苗接种在诱导免疫记忆和预防癌症复发方面表现出色。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd08/11982544/3606c5bbb226/41467_2025_58289_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd08/11982544/0fa3864d8337/41467_2025_58289_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd08/11982544/3f0e70d5b999/41467_2025_58289_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd08/11982544/01d80c0e50d6/41467_2025_58289_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd08/11982544/2985dec555df/41467_2025_58289_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd08/11982544/6208fade433d/41467_2025_58289_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd08/11982544/30cc85523bb3/41467_2025_58289_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd08/11982544/3606c5bbb226/41467_2025_58289_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd08/11982544/0fa3864d8337/41467_2025_58289_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd08/11982544/3f0e70d5b999/41467_2025_58289_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd08/11982544/01d80c0e50d6/41467_2025_58289_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd08/11982544/2985dec555df/41467_2025_58289_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd08/11982544/6208fade433d/41467_2025_58289_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd08/11982544/30cc85523bb3/41467_2025_58289_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd08/11982544/3606c5bbb226/41467_2025_58289_Fig7_HTML.jpg

相似文献

[1]
Immunotherapy with conventional type-1 dendritic cells induces immune memory and limits tumor relapse.

Nat Commun. 2025-4-9

[2]
Effective cancer immunotherapy by natural mouse conventional type-1 dendritic cells bearing dead tumor antigen.

J Immunother Cancer. 2019-4-8

[3]
Induction of Progenitor Exhausted Tissue-Resident Memory CD8 T Cells Upon Typhi Porins Adjuvant Immunization Correlates With Melanoma Control and Anti-PD-1 Immunotherapy Cooperation.

Front Immunol. 2020

[4]
Prophylactic dendritic cell vaccination controls pancreatic cancer growth in a mouse model.

Cytotherapy. 2020-1

[5]
Nonspecific CD4(+) T cells with uptake of antigen-specific dendritic cell-released exosomes stimulate antigen-specific CD8(+) CTL responses and long-term T cell memory.

J Leukoc Biol. 2007-10

[6]
Dendritic cells charged with apoptotic tumor cells induce long-lived protective CD4+ and CD8+ T cell immunity against B16 melanoma.

J Immunol. 2003-12-1

[7]
TCF1-positive and TCF1-negative TRM CD8 T cell subsets and cDC1s orchestrate melanoma protection and immunotherapy response.

J Immunother Cancer. 2024-7-5

[8]
CXCR6 deficiency impairs cancer vaccine efficacy and CD8 resident memory T-cell recruitment in head and neck and lung tumors.

J Immunother Cancer. 2021-3

[9]
Dendritic Cell Vaccination in Metastatic Melanoma Turns "Non-T Cell Inflamed" Into "T-Cell Inflamed" Tumors.

Front Immunol. 2019-10-9

[10]
Optimizing dendritic cell vaccine for immunotherapy in multiple myeloma: tumour lysates are more potent tumour antigens than idiotype protein to promote anti-tumour immunity.

Clin Exp Immunol. 2012-11

本文引用的文献

[1]
Intratumoral immune triads are required for immunotherapy-mediated elimination of solid tumors.

Cancer Cell. 2024-7-8

[2]
Adjuvant dendritic cell therapy in stage IIIB/C melanoma: the MIND-DC randomized phase III trial.

Nat Commun. 2024-2-23

[3]
Dendritic cells as orchestrators of anticancer immunity and immunotherapy.

Nat Rev Clin Oncol. 2024-4

[4]
Intratumoral dendritic cell-CD4 T helper cell niches enable CD8 T cell differentiation following PD-1 blockade in hepatocellular carcinoma.

Nat Med. 2023-6

[5]
Tumor-infiltrating regulatory T cells as targets of cancer immunotherapy.

Cancer Cell. 2023-3-13

[6]
Locally sourced: site-specific immune barriers to metastasis.

Nat Rev Immunol. 2023-8

[7]
CD4 helper T cells endow cDC1 with cancer-impeding functions in the human tumor micro-environment.

Nat Commun. 2023-1-13

[8]
Immunological responses to adjuvant vaccination with combined CD1c myeloid and plasmacytoid dendritic cells in stage III melanoma patients.

Oncoimmunology. 2022

[9]
Metastatic recurrence in colorectal cancer arises from residual EMP1 cells.

Nature. 2022-11

[10]
Depletion of Conventional Type-1 Dendritic Cells in Established Tumors Suppresses Immunotherapy Efficacy.

Cancer Res. 2022-12-2

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