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CC配体趋化因子家族成员CCL17/CCL22可预测头颈部鳞状细胞癌患者的生存情况及对免疫检查点阻断疗法的反应。

The CC ligand chemokine family members CCL17/CCL22 predict the survival and response to immune checkpoint blockade therapy of patients with head and neck squamous cell carcinoma.

作者信息

Zhou Wenkai, Zhang Xu, Feng Yisheng, Zhang Yu, Liu Zheqi

机构信息

Department of Oral Maxillofacial-Head Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai 200011, China.

Department of Oral Maxillofacial-Head Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai 200011, China.

出版信息

Curr Probl Cancer. 2022 Dec;46(6):100896. doi: 10.1016/j.currproblcancer.2022.100896. Epub 2022 Sep 21.

Abstract

Head and neck squamous cell carcinoma (HNSCC) is considered an immunosuppressive malignancy. Cross-talk between cancer cells and immune cells is modulated in part by CC ligand (CCL) chemokines, having a major effect on tumor progression. However, the predictive value and function of CCL family members in HNSCC have not been elucidated. Here, the predictive value of CCL members in cancer prognosis and Immune checkpoint blockade therapy response was investigated. CCL17 and CCL22 were screened as the key CCL chemokines in HNSCC through co-expression analysis. Further, the correlation between CCL17/CCL22 expression and cancer immune infiltration were evaluated based on TIMER and were validated by a set of scRNA-seq data. Moreover, the expression level of CCL17/CCL22 we evaluated to predict the response to Immune checkpoint blockade therapy in a panel of cancer types by using the TIDE database. Results indicated that CCL17/CCL22 had a high co-expression correlation and had a marginally statistical significance with the overall survival in HNSCC patients (P value = 0.057 and 0.055, respectively). Our findings showed high expression of CCL17/CCL22 was positively correlated with CD4 T cell infiltration levels in HNSCCs and activate mTORC1 signaling pathway in CD4 T cells. Further analysis from TIDE showed the high expression of CCL17/CCL22 might predict favorable responses to immune checkpoint blockade therapy in HNSCC patients. These findings provide an insight into the predictive roles of CCL17/CCL22 in HNSCC.

摘要

头颈部鳞状细胞癌(HNSCC)被认为是一种免疫抑制性恶性肿瘤。癌细胞与免疫细胞之间的相互作用部分受CC配体(CCL)趋化因子调节,对肿瘤进展有重大影响。然而,CCL家族成员在HNSCC中的预测价值和功能尚未阐明。在此,研究了CCL成员在癌症预后和免疫检查点阻断治疗反应中的预测价值。通过共表达分析筛选出CCL17和CCL22作为HNSCC中的关键CCL趋化因子。此外,基于TIMER评估了CCL17/CCL22表达与癌症免疫浸润之间的相关性,并通过一组单细胞RNA测序数据进行了验证。此外,我们利用TIDE数据库评估了CCL17/CCL22的表达水平,以预测一组癌症类型对免疫检查点阻断治疗的反应。结果表明,CCL17/CCL22具有高度共表达相关性,与HNSCC患者的总生存期具有边缘统计学意义(P值分别为0.057和0.055)。我们的研究结果表明,CCL17/CCL22的高表达与HNSCC中CD4 T细胞浸润水平呈正相关,并激活CD4 T细胞中的mTORC1信号通路。TIDE的进一步分析表明,CCL17/CCL22的高表达可能预测HNSCC患者对免疫检查点阻断治疗有良好反应。这些发现为CCL17/CCL22在HNSCC中的预测作用提供了见解。

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