LRP2 and DOCK8 Are Potential Antigens for mRNA Vaccine Development in Immunologically 'Cold' KIRC Tumours.
LRP2 and DOCK8 Are Potential Antigens for mRNA Vaccine Development in Immunologically 'Cold' KIRC Tumours.
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DOI：
10.3390/vaccines11020396
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发表时间：
2023-02-09
期刊：
影响因子：
7.8
通讯作者：
Ouyang Y
中科院分区：
文献类型：
--
作者：
Zhang S;Xia K;Chang Y;Wei Y;Xiong Y;Tang F;Peng J;Ouyang Y
基于mRNA的肿瘤疫苗的施用被认为是肿瘤免疫治疗中有前途的策略，尽管其针对肾透明细胞癌（KIRC）的应用仍处于起步阶段。本研究的目的是确定潜在的抗原，并进一步选择合适的患者进行疫苗接种。基因表达数据和临床信息从Gene Expression Omnibus（GEO）和The Cancer Genome Atlas（TCGA）数据库检索。GEPIA 2用于评估所选抗原的预后价值。TIMER法分析抗原呈递细胞浸润与抗原表达的关系，无监督聚类分析法确定免疫亚型。在KIRC中鉴定了与预后和肿瘤浸润性抗原呈递细胞相关的肿瘤抗原LRP 2和DOCK 8。总共鉴定了六种免疫亚型，免疫亚型1-4（IS 1 -4）肿瘤患者具有免疫“冷”表型，肿瘤突变负荷较高，生存率较低。此外，这些免疫亚型在免疫检查点和免疫原性细胞死亡调节剂的表达方面显示出显著差异。最后，KIRC的免疫景观揭示了个体患者中免疫相关的细胞成分。本研究提示，LRP 2和DOCK 8是mRNA疫苗开发中潜在的KIRC抗原，免疫亚型IS 1 -4的患者适合接种。
The administration of mRNA-based tumour vaccines is considered a promising strategy in tumour immunotherapy, although its application against kidney renal clear cell carcinoma (KIRC) is still at its infancy stage. The purpose of this study was to identify potential antigens and to further select suitable patients for vaccination. Gene expression data and clinical information were retrieved from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. GEPIA2 was used to evaluate the prognostic value of selected antigens. The relationship of antigens presenting cell infiltration with antigen expression was evaluated by TIMER, and immune subtypes were determined using unsupervised cluster analysis. Tumour antigens LRP2 and DOCK8, which are associated with prognosis and tumour-infiltrating antigen-presenting cells, were identified in KIRC. A total of six immune subtypes were identified, and patients with immune subtype 1–4 (IS1–4) tumours had an immune ‘cold’ phenotype, a higher tumour mutation burden, and poor survival. Moreover, these immune subtypes showed significant differences in the expression of immune checkpoint and immunogenic cell death modulators. Finally, the immune landscape of KIRC revealed the immune-related cell components in individual patients. This study suggests that LRP2 and DOCK8 are potential KIRC antigens in the development of mRNA vaccines, and patients with immune subtypes IS1–4 are suitable for vaccination.
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DOI：
10.1038/nrd.2017.243
发表时间：
2018-04
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
Pardi N;Hogan MJ;Porter FW;Weissman D
通讯作者：
Weissman D
影响因子：
12.4
作者：
Rittig, Susanne M.;Haentschel, Maik;Brossart, Peter
通讯作者：
Brossart, Peter
影响因子：
64.5
作者：
Rooney MS;Shukla SA;Wu CJ;Getz G;Hacohen N
通讯作者：
Hacohen N
影响因子：
14
作者：
Islam MA;Rice J;Reesor E;Zope H;Tao W;Lim M;Ding J;Chen Y;Aduluso D;Zetter BR;Farokhzad OC;Shi J
通讯作者：
Shi J
影响因子：
4.6
作者：
Hsu, Jacob Shujui;Zhang, Ruizhong;Garcia-Barcelo, Maria-Merce
通讯作者：
Garcia-Barcelo, Maria-Merce