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Identification of neoantigens and immunological subtypes in clear cell renal cell carcinoma for mRNA vaccine development and patient selection

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机构: [1]School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, Guangdong, China. [2]Department of Epidemiology, School of Public Health, Southern Medical University, Guangzhou 510515, Guangdong, China. [3]Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, Guangdong, China. [4]Department of pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, China. [5]The Affiliated TCM Hospital of Guangzhou Medical University, Guangzhou 510130, Guangdong, China
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关键词: ccRCC mRNA vaccine tumor antigens immune cancer subtypes cancer therapy

摘要:
Clear cell renal cell carcinoma (ccRCC) is a common urological malignancy with diverse histological types. This study aimed to detect neoantigens in ccRCC to develop mRNA vaccines and distinguish between ccRCC immunological subtypes for construction of an immune landscape to select patients suitable for vaccination. Using The Cancer Genome Atlas SpliceSeq database, The Cancer Genome Atlas, and the International Cancer Genome Consortium cohorts, we comprehensively analysed potential tumour antigens of ccRCC associated with aberrant alternative splicing, somatic mutation, nonsense-mediated mRNA decay factors, antigen-presenting cells, and overall survival. Immune subtypes (C1/C2) and nine immune gene modules of ccRCC were identified by consistency clustering and weighted correlation network analysis. The immune landscape as well as molecular and cellular characteristics of immunotypes were assessed. Rho-guanine nucleotide exchange factor 3 (ARHGEF3) was identified as a new ccRCC antigen for development of an mRNA vaccine. A higher tumour mutation burden, differential expression of immune checkpoints, and immunogenic cell death were observed in cases with the C2 immunotype. Cellular characteristics increased the complexity of the immune environment, and worse outcomes were observed in ccRCC cases with the C2 immunotype. We constructed the immune landscape for selecting patients with the C2 immunotype suitable for vaccination.

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大类 | 2 区 医学
小类 | 3 区 老年医学 3 区 细胞生物学
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第一作者机构: [1]School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, Guangdong, China.
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