A Tumor-Infiltration CD8+ T Cell-Based Gene Signature for Facilitating the Prognosis and Estimation of Immunization Responses in HPV+ Head and Neck Squamous Cell Cancer.
A Tumor-Infiltration CD8+ T Cell-Based Gene Signature for Facilitating the Prognosis and Estimation of Immunization Responses in HPV+ Head and Neck Squamous Cell Cancer.
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DOI：
10.3389/fonc.2021.749398
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发表时间：
2021
影响因子：
4.7
通讯作者：
Song J
中科院分区：
文献类型：
--
作者：
Wu Y;Meng L;Cai K;Zhao J;He S;Shen J;Wei Q;Wang Z;Sooranna S;Li H;Song J
CD8+T细胞在获得性免疫应答中起着至关重要的作用，与杀伤肿瘤细胞的免疫应答密切相关。了解肿瘤浸润性CD8+T细胞在HPV阳性和HPV-头颈部鳞状细胞癌(HNSCC)患者中的作用，对于预测他们的预后以及他们对免疫相关治疗的反应至关重要。用HNSCC单细胞转录组筛选以CD8+T细胞为基础的差异表达基因。建立了与CD8+T细胞相关的基因标记，并用癌症基因组图谱数据集进行了验证，以期预测HNSCC患者的预后。计算了HNSCC病例的风险评分，并将其归类为高风险或低风险队列。采用Kaplan-Meier生存曲线和多因素Cox回归分析与预后相关的危险评分数据。此外，还探讨了利用基因图谱预测免疫相关治疗反应的可能性。从单细胞RNA测序中筛选出4个基因(ACAP1、ANKRD28、C12orf75和M6PR)的基因特征。研究表明，这些基因可以预测HPV+HNSCC患者的总存活率。此外，考虑到临床特点，高危和低危HPV+HNSCC患者在免疫后CD8+T细胞浸润方面也有明显差异。这与他们的免疫治疗反应有关。我们的工作为解释当前免疫检查点抑制物质对HPV+HNSCC患者的限制性反应提供了见解。提出了一种新的预测预后和免疫相关治疗反应的遗传特征。这将为HPV+HNSCC患者提供潜在的新的治疗机会。
CD8+ T cells, which play a vital role in response to adaptive immunity, are closely related to the immunization responses to kill tumor cells. Understanding the effects exerted by tumor-infiltrated CD8+ T cells in HPV+ and HPV- head and neck squamous cell carcinoma (HNSCC) patients is critical for predicting their prognosis as well as their responses towards immunization-related therapy. HNSCC single cell transcriptome was used to screen for differentially expressed genes (DEGs) based on CD8+ T cells. A gene signature associated with CD8+ T cells was built and verified with the cancer genome atlas dataset with a view to predicting the prognosis of HNSCC patients. Risk scores were calculated for HNSCC cases and categorized into either high- or low-risk cohorts. The prognosis-correlated data of the risk scores were analyzed by using Kaplan-Meier survival curves and multi-variate Cox regression plots. In addition, the possibility of using the genetic profiles to predict responses toward immunization-related therapy was explored. From the DEGs screened from the sequencing of single-cell RNA, a gene signature of 4 genes (ACAP1, ANKRD28, C12orf75, and M6PR) were identified. It was seen that these genes could predict overall survival in HPV+ HNSCC patients. In addition, high- and low-risk HPV+ HNSCC patients showed marked differences in their CD8+ T-cell infiltration due to immunization when clinical characteristics were taken into consideration. This correlated with their immunization therapy responses. Our work provides insights into explaining the restricted responses of current immunization checkpoint inhibiting substances in HPV+ HNSCC patients. A novel genetic signature to predict the prognosis and immunization-correlated therapeutic responses is presented. This will provide potential new therapeutic opportunities for HPV+ HNSCC patients.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
1.3
作者：
Therneau, TM;Li, HZ
通讯作者：
Li, HZ
DOI：
10.1056/nejmoa0912217
发表时间：
2010-07-01
期刊：
The New England journal of medicine
影响因子：
--
作者：
Ang KK;Harris J;Wheeler R;Weber R;Rosenthal DI;Nguyen-Tân PF;Westra WH;Chung CH;Jordan RC;Lu C;Kim H;Axelrod R;Silverman CC;Redmond KP;Gillison ML
通讯作者：
Gillison ML
影响因子：
6.4
作者：
Carvalho, AL;Nishimoto, IN;Kowalski, LP
通讯作者：
Kowalski, LP
影响因子：
12.3
作者：
Becht E;Giraldo NA;Lacroix L;Buttard B;Elarouci N;Petitprez F;Selves J;Laurent-Puig P;Sautès-Fridman C;Fridman WH;de Reyniès A
通讯作者：
de Reyniès A