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

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

doi:10.1016/j.currproblcancer.2022.100896

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

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

Authors

Wenkai Zhou¹, Xu Zhang¹, Yisheng Feng¹, Yu Zhang², Zheqi Liu³

Affiliations

¹ 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.
² 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. Electronic address: zhyzhy1818@sjtu.edu.cn.
³ 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. Electronic address: 734672500@sjtu.edu.cn.

PMID: 36167005
DOI: 10.1016/j.currproblcancer.2022.100896

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.

Keywords: CCL; HNSCC; immune checkpoint blockade; immune microenvironment; single-cell RNA sequencing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Chemokine CCL17
Chemokine CCL22
Chemokines, CC*
Head and Neck Neoplasms* / drug therapy
Humans
Immune Checkpoint Inhibitors / pharmacology
Immune Checkpoint Inhibitors / therapeutic use
Ligands
Squamous Cell Carcinoma of Head and Neck / drug therapy

Substances

Chemokines, CC
Immune Checkpoint Inhibitors
Ligands
CCL17 protein, human
Chemokine CCL17
CCL22 protein, human
Chemokine CCL22