Syngeneic B16-F1 cells are more efficient than allogeneic Cloudman cells as antigen source in DC-based vaccination in the B16-F1 murine melanoma model.
Syngeneic B16-F1 cells are more efficient than allogeneic Cloudman cells as antigen source in DC-based vaccination in the B16-F1 murine melanoma model.
复制标题
在 B16-F1 鼠黑色素瘤模型中基于 DC 的疫苗接种中，同基因 B16-F1 细胞作为抗原来源比同种异体 Cloudman 细胞更有效。
DOI：
10.1016/j.vaccine.2019.07.018
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发表时间：
2019
期刊：
影响因子：
5.5
通讯作者：
Mordoh,José
中科院分区：
文献类型：
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作者：
MacKeon,Soledad;Bentivegna,Sofía;Levy,EstrellaM;Marks,MichaelS;Mantegazza,AdrianaR;Wainstok,Rosa;Mordoh,José
在癌症疫苗接种中获得相关结果的一个主要障碍是缺乏免疫原性抗原的鉴定。以树突状细胞（DC）为基础的肿瘤疫苗可预防肿瘤接种，但抗原选择对抗肿瘤保护的作用尚不清楚。当使用辐照的同基因肿瘤细胞装载dc时，提供肿瘤自身抗原，包括肿瘤相关抗原（TAAs）和肿瘤突变产生的新抗原。另一方面，异体肿瘤细胞只能提供共享的TAAs。为了评估每种来源在保护性疫苗接种中的优势，我们在C57BL/6小鼠中分析了将辐照的同源B16-F1或同种异体Cloudman黑色素瘤细胞加载dc的效果；通过全外显子组测序和RNAseq对两株细胞系进行了鉴定。来自两种辐照细胞系的肿瘤细胞成分被dc有效地内化，并运输到mhc - II类阳性管泡室（MIICs）。尽管Cloudman和B16-F1细胞共享黑色素细胞分化抗原（mda）、癌睾丸抗原（cta）和其他TAAs的表达，但负载同种异体辐照的Cloudman细胞（DC-ApoNecALLO）的dc诱导了部分有效的抗黑色素瘤保护作用。负载同源B16-F1细胞（DC-ApoNecSYN）的dc建立了更有效和持久的保护，并诱导了体液抗b16f1反应，这表明需要新表位来诱导持久的保护。
A major obstacle to obtaining relevant results in cancer vaccination has been the lack of identification of immunogenic antigens. Dendritic cell (DC)-based cancer vaccines used preventively may afford protection against tumor inoculation, but the effect of antigen choice on anti-tumor protection is not clear. When using irradiated syngeneic tumor cells to load DCs, tumor self-antigens are provided, including tumor-associated antigens (TAAs) and neoantigens generated by tumor mutations. On the other hand, allogeneic tumor cells could only supply shared TAAs. To assess the advantages of each source in protective vaccination, we analyzed in C57BL/6 mice the effect of loading DCs with irradiated syngeneic B16-F1 or allogeneic Cloudman melanoma cells; both cell lines were characterized by whole exome sequencing and RNAseq. Tumor cell components from the two irradiated cell lines were efficiently internalized by DCs, and transported to MHC-class II positive tubulovesicular compartments (MIICs). DCs loaded with allogeneic irradiated Cloudman cells (DC-ApoNecALLO) induced a partially effective anti-melanoma protection, although Cloudman and B16-F1 cells share the expression of melanocyte differentiation antigens (MDAs), cancer-testis antigens (CTAs) and other TAAs. DCs loaded with syngeneic B16-F1 cells (DC-ApoNecSYN) established a more potent and long-lasting protection and induced a humoral anti-B16F1 response, thus suggesting that neoepitopes are needed for inducing long-lasting protection.