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黑素瘤干细胞疫苗可诱导针对黑素瘤的有效肿瘤免疫。

Melanoma stem cell vaccine induces effective tumor immunity against melanoma.

机构信息

Academic Affairs Office, Jilin Medical University, Jilin, China.

Department of Cadre Ward, The First Hospital of Jilin University, Changchun, China.

出版信息

Hum Vaccin Immunother. 2023 Dec 31;19(1):2158670. doi: 10.1080/21645515.2022.2158670. Epub 2023 Apr 17.

DOI:10.1080/21645515.2022.2158670
PMID:37067182
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10114997/
Abstract

Melanoma stem cells (MSCs)-based vaccine strategies have been a potent immunotherapeutic approach for melanoma treatment, which aimed at inducing specific anti-tumor immunity and targeting cancer stem-like cells. As the main cancer-fighting immune cells, CD8T cells play an important role in vaccine-induced antitumor immunity. Here, we developed a novel MSC vaccine that induces CD8T cells to target melanoma stem cells specifically. The MSC vaccine was prepared for our study in order to determine the effectiveness of antitumor immunity. The proportion and activity of CD8T cells were examined in the spleen after immunization, in particular, the expression and cytotoxicity of the immune checkpoint of spleen lymphocytes were detected by flow cytometry and ELISA, moreover, tumor size and the number of lung metastasis nodules were observed and the specific killing effect of the vaccine was evaluated in immunized mice. We found that the MSC vaccine could promote DCs maturation, activate CD8T cells, suppress the expression of CTLA-4, PD-1, and Tim-3, and increase the expression of IFN-γ and GzmB of CD8T cells. Melanoma growth and metastasis were inhibited by the vaccine's specific targeted killing effect. The vaccines based on melanoma stem cells (MSCs) delay the progression of melanoma by inducing anti-tumor immune responses in CD8T cells.

摘要

黑色素瘤干细胞(MSCs)疫苗策略一直是治疗黑色素瘤的一种有效的免疫治疗方法,旨在诱导特异性抗肿瘤免疫和靶向肿瘤干细胞样细胞。作为主要的抗癌免疫细胞,CD8T 细胞在疫苗诱导的抗肿瘤免疫中发挥重要作用。在这里,我们开发了一种新型的 MSC 疫苗,可诱导 CD8T 细胞特异性靶向黑色素瘤干细胞。我们研究中制备的 MSC 疫苗旨在确定抗肿瘤免疫的有效性。在免疫后检测了脾中 CD8T 细胞的比例和活性,特别通过流式细胞术和 ELISA 检测了脾淋巴细胞免疫检查点的表达和细胞毒性,此外,观察了肿瘤大小和肺转移结节的数量,并评估了疫苗在免疫小鼠中的特异性杀伤作用。我们发现 MSC 疫苗可以促进 DC 成熟,激活 CD8T 细胞,抑制 CTLA-4、PD-1 和 Tim-3 的表达,增加 CD8T 细胞中 IFN-γ 和 GzmB 的表达。疫苗的特异性靶向杀伤作用抑制了黑色素瘤的生长和转移。基于黑色素瘤干细胞(MSCs)的疫苗通过诱导 CD8T 细胞的抗肿瘤免疫反应来延缓黑色素瘤的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ab/10114997/01a094e0f312/KHVI_A_2158670_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ab/10114997/e8bd7af8970b/KHVI_A_2158670_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ab/10114997/5ada7fb41001/KHVI_A_2158670_F0002a_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ab/10114997/b716d2e17ad3/KHVI_A_2158670_F0002b_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ab/10114997/1a5143e85d36/KHVI_A_2158670_F0003a_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ab/10114997/19050ae939d3/KHVI_A_2158670_F0003b_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ab/10114997/f6c5dfbbac6b/KHVI_A_2158670_F0004a_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ab/10114997/3153c4d60848/KHVI_A_2158670_F0004b_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ab/10114997/fb47d34e5ec9/KHVI_A_2158670_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ab/10114997/01a094e0f312/KHVI_A_2158670_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ab/10114997/e8bd7af8970b/KHVI_A_2158670_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ab/10114997/5ada7fb41001/KHVI_A_2158670_F0002a_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ab/10114997/b716d2e17ad3/KHVI_A_2158670_F0002b_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ab/10114997/1a5143e85d36/KHVI_A_2158670_F0003a_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ab/10114997/19050ae939d3/KHVI_A_2158670_F0003b_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ab/10114997/f6c5dfbbac6b/KHVI_A_2158670_F0004a_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ab/10114997/3153c4d60848/KHVI_A_2158670_F0004b_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ab/10114997/fb47d34e5ec9/KHVI_A_2158670_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ab/10114997/01a094e0f312/KHVI_A_2158670_F0006_OC.jpg

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