PDF(Pubmed)
Abstract：
UNASSIGNED: The human leukocyte antigen complex (HLA) is essential for inducing specific immune responses to cancer by presenting tumor-associated peptides (TAP) to T cells. Overexpressed tumor associated antigens, mainly cancer-testis antigens (CTA), are outlined as essential targets for immunotherapy in oropharyngeal squamous cell carcinoma (OPSCC). This study assessed the degree to which presentation, gene expression, and antibody response (AR) of TAP, mainly CTA, are correlated in OPSCC patients to evaluate their potential as immunotherapy targets.
UNASSIGNED: Snap-frozen tumor (NLigand/RNA=40), healthy mucosa (NRNA=6), and healthy tonsils (NLigand=5) samples were obtained. RNA-Seq was performed using Illumina HiSeq 2500/NovaSeq 6000 and whole exome sequencing (WES) utilizing NextSeq500. HLA ligands were isolated from tumor tissue using immunoaffinity purification, UHPLC, and analyzed by tandem MS. Antibodies were measured in serum (NAb=27) utilizing the KREX™ CT262 protein array. Data analysis focused on 312 proteins (KREX™ CT262 panel + overexpressed self-proteins).
UNASSIGNED: 183 and 94 of HLA class I and II TAP were identified by comparative profiling with healthy tonsils. Genes from 26 TAP were overexpressed in tumors compared to healthy mucosa (LFC>1; FDR<0.05). Low concordance (r=0.25; p<0.0001) was found between upregulated mRNA and class I TAP. The specific mode of correlation of TAP was found to be dependent on clinical parameters. A lack of correlation was observed both between mRNA and class II TAP, as well as between class II tumor-unique TAP (TAP-U) presentation and antibody response (AR) levels.
UNASSIGNED: This study demonstrates that focusing exclusively on gene transcript levels fails to capture the full extent of TAP presentation in OPSCC. Furthermore, our findings reveal that although CTA are presented at relatively low levels, a few CTA TAP-U show potential as targets for immunotherapy.
UNASSIGNED: Snap-frozen tumor (NLigand/RNA=40), healthy mucosa (NRNA=6), and healthy tonsils (NLigand=5) samples were obtained. RNA-Seq was performed using Illumina HiSeq 2500/NovaSeq 6000 and whole exome sequencing (WES) utilizing NextSeq500. HLA ligands were isolated from tumor tissue using immunoaffinity purification, UHPLC, and analyzed by tandem MS. Antibodies were measured in serum (NAb=27) utilizing the KREX™ CT262 protein array. Data analysis focused on 312 proteins (KREX™ CT262 panel + overexpressed self-proteins).
UNASSIGNED: 183 and 94 of HLA class I and II TAP were identified by comparative profiling with healthy tonsils. Genes from 26 TAP were overexpressed in tumors compared to healthy mucosa (LFC>1; FDR<0.05). Low concordance (r=0.25; p<0.0001) was found between upregulated mRNA and class I TAP. The specific mode of correlation of TAP was found to be dependent on clinical parameters. A lack of correlation was observed both between mRNA and class II TAP, as well as between class II tumor-unique TAP (TAP-U) presentation and antibody response (AR) levels.
UNASSIGNED: This study demonstrates that focusing exclusively on gene transcript levels fails to capture the full extent of TAP presentation in OPSCC. Furthermore, our findings reveal that although CTA are presented at relatively low levels, a few CTA TAP-U show potential as targets for immunotherapy.
摘要：
人白细胞抗原复合物(HLA)对于通过将肿瘤相关肽(TAP)呈递至T细胞来诱导针对癌症的特异性免疫应答是必需的。过表达肿瘤相关抗原,主要是癌症-睾丸抗原（CTA），概述了作为口咽鳞状细胞癌（OPSCC）免疫治疗的基本靶标。这项研究评估了演示文稿的程度，基因表达，和TAP的抗体反应（AR），主要是CTA,与OPSCC患者相关，以评估其作为免疫治疗靶标的潜力。
■速冻肿瘤（NLigand/RNA=40），健康粘膜（NRNA=6），并获得健康扁桃体(NLigand=5)样品。使用IlluminaHiSeq2500/NovaSeq6000进行RNA-Seq,并利用NextSeq500进行全外显子组测序(WES)。使用免疫亲和纯化从肿瘤组织中分离HLA配体，UHPLC,并由串联MS分析。使用KREX™CT262蛋白阵列在血清(NAb=27)中测量抗体。数据分析集中于312种蛋白质(KREX™CT262组+过表达的自身蛋白质)。
■通过与健康扁桃体的比较分析鉴定了HLAI类和II类TAP的183和94。与健康粘膜相比,来自26TAP的基因在肿瘤中过表达(LFC>1;FDR<0.05)。在上调的mRNA和I类TAP之间发现低一致性(r=0.25;p<0.0001)。发现TAP的特定相关性模式取决于临床参数。mRNA和II类TAP之间均缺乏相关性，以及II类肿瘤独特的TAP（TAP-U）呈递和抗体反应（AR）水平之间。
■这项研究表明，仅关注基因转录水平无法捕获OPSCC中TAP呈递的全部程度。此外，我们的研究结果表明，尽管CTA的水平相对较低，一些CTATAP-U显示出作为免疫治疗靶点的潜力.
■速冻肿瘤（NLigand/RNA=40），健康粘膜（NRNA=6），并获得健康扁桃体(NLigand=5)样品。使用IlluminaHiSeq2500/NovaSeq6000进行RNA-Seq,并利用NextSeq500进行全外显子组测序(WES)。使用免疫亲和纯化从肿瘤组织中分离HLA配体，UHPLC,并由串联MS分析。使用KREX™CT262蛋白阵列在血清(NAb=27)中测量抗体。数据分析集中于312种蛋白质(KREX™CT262组+过表达的自身蛋白质)。
■通过与健康扁桃体的比较分析鉴定了HLAI类和II类TAP的183和94。与健康粘膜相比,来自26TAP的基因在肿瘤中过表达(LFC>1;FDR<0.05)。在上调的mRNA和I类TAP之间发现低一致性(r=0.25;p<0.0001)。发现TAP的特定相关性模式取决于临床参数。mRNA和II类TAP之间均缺乏相关性，以及II类肿瘤独特的TAP（TAP-U）呈递和抗体反应（AR）水平之间。
■这项研究表明，仅关注基因转录水平无法捕获OPSCC中TAP呈递的全部程度。此外，我们的研究结果表明，尽管CTA的水平相对较低，一些CTATAP-U显示出作为免疫治疗靶点的潜力.
