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免疫治疗后免疫的袋獾面部肿瘤疾病消退。

Regression of devil facial tumour disease following immunotherapy in immunised Tasmanian devils.

机构信息

Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania 7000, Australia.

Faculty of Veterinary Science, University of Sydney, Sydney, New South Wales 2006, Australia.

出版信息

Sci Rep. 2017 Mar 9;7:43827. doi: 10.1038/srep43827.

DOI:10.1038/srep43827
PMID:28276463
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5343465/
Abstract

Devil facial tumour disease (DFTD) is a transmissible cancer devastating the Tasmanian devil (Sarcophilus harrisii) population. The cancer cell is the 'infectious' agent transmitted as an allograft by biting. Animals usually die within a few months with no evidence of antibody or immune cell responses against the DFTD allograft. This lack of anti-tumour immunity is attributed to an absence of cell surface major histocompatibility complex (MHC)-I molecule expression. While the endangerment of the devil population precludes experimentation on large experimental groups, those examined in our study indicated that immunisation and immunotherapy with DFTD cells expressing surface MHC-I corresponded with effective anti-tumour responses. Tumour engraftment did not occur in one of the five immunised Tasmanian devils, and regression followed therapy of experimentally induced DFTD tumours in three Tasmanian devils. Regression correlated with immune cell infiltration and antibody responses against DFTD cells. These data support the concept that immunisation of devils with DFTD cancer cells can successfully induce humoral responses against DFTD and trigger immune-mediated regression of established tumours. Our findings support the feasibility of a protective DFTD vaccine and ultimately the preservation of the species.

摘要

恶魔面部肿瘤病(DFTD)是一种具有传染性的癌症,正在摧毁塔斯马尼亚恶魔(Sarcophilus harrisii)种群。癌细胞是通过咬伤传播的“传染性”异体移植物。动物通常在几个月内死亡,没有针对 DFTD 异体移植物的抗体或免疫细胞反应的证据。这种缺乏抗肿瘤免疫力归因于缺乏细胞表面主要组织相容性复合体(MHC)-I 分子的表达。虽然恶魔种群的濒危状况排除了对大型实验组进行实验,但我们研究中检查的那些表明,用表达表面 MHC-I 的 DFTD 细胞进行免疫接种和免疫治疗与有效的抗肿瘤反应相对应。在五名免疫的塔斯马尼亚恶魔中,有一名没有发生肿瘤移植,在三名塔斯马尼亚恶魔中,实验诱导的 DFTD 肿瘤的治疗后出现了肿瘤消退。消退与免疫细胞浸润和针对 DFTD 细胞的抗体反应相关。这些数据支持了这样的概念,即用 DFTD 癌细胞对恶魔进行免疫接种可以成功诱导针对 DFTD 的体液反应,并触发已建立的肿瘤的免疫介导消退。我们的发现支持了一种保护性 DFTD 疫苗的可行性,并最终保护了该物种。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35ca/5343465/0e396643dc7e/srep43827-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35ca/5343465/89325a14c513/srep43827-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35ca/5343465/7db4af2a2663/srep43827-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35ca/5343465/c181e4c11329/srep43827-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35ca/5343465/0e396643dc7e/srep43827-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35ca/5343465/89325a14c513/srep43827-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35ca/5343465/7db4af2a2663/srep43827-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35ca/5343465/c181e4c11329/srep43827-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35ca/5343465/0e396643dc7e/srep43827-f4.jpg

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PD-L1 Is Not Constitutively Expressed on Tasmanian Devil Facial Tumor Cells but Is Strongly Upregulated in Response to IFN-γ and Can Be Expressed in the Tumor Microenvironment.程序性死亡配体1(PD-L1)在袋獾面部肿瘤细胞上并非组成性表达,但在干扰素-γ的作用下会强烈上调,且可在肿瘤微环境中表达。
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Widespread transmission of independent cancer lineages within multiple bivalve species.
Evol Appl. 2025 Apr 1;18(4):e70091. doi: 10.1111/eva.70091. eCollection 2025 Apr.
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Complex associations between cancer progression and immune gene expression reveals early influence of transmissible cancer on Tasmanian devils.癌症进展与免疫基因表达之间的复杂关联揭示了传染性癌症对塔斯马尼亚恶魔的早期影响。
Front Immunol. 2024 Mar 7;15:1286352. doi: 10.3389/fimmu.2024.1286352. eCollection 2024.
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