Dissecting the heterogeneity of the microenvironment in primary and recurrent nasopharyngeal carcinomas using single-cell RNA sequencing

Wen-Sa Peng; Xin Zhou; Wen-Bin Yan; Yu-Jiao Li; Cheng-Run Du; Xiao-Shen Wang; Chun-Ying Shen; Qi-Feng Wang; Hong-Mei Ying; Xue-Guan Lu; Ting-Ting Xu; Chao-Su Hu

doi:10.1080/2162402X.2022.2026583

Dissecting the heterogeneity of the microenvironment in primary and recurrent nasopharyngeal carcinomas using single-cell RNA sequencing

Oncoimmunology. 2022 Jan 25;11(1):2026583. doi: 10.1080/2162402X.2022.2026583. eCollection 2022.

Authors

Wen-Sa Peng^{1

2}, Xin Zhou^{1

2}, Wen-Bin Yan^{1

2}, Yu-Jiao Li^{1

2}, Cheng-Run Du^{1

2}, Xiao-Shen Wang³, Chun-Ying Shen^{1

2}, Qi-Feng Wang^{2

4}, Hong-Mei Ying^{1

2}, Xue-Guan Lu^{1

2}, Ting-Ting Xu^{1

2}, Chao-Su Hu^{1

2}

Affiliations

¹ Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
² Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
³ Department of Radiation Oncology, Eye, Ear, Nose & Throat Hospital of Fudan University, Shanghai, China.
⁴ Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.

Abstract

Nasopharyngeal carcinoma (NPC) has a 10-15% recurrence rate, while no long term or durable treatment options are currently available. Single-cell profiling in recurrent NPC (rNPC) may aid in designing effective anticancer therapies, including immunotherapies. For the first time, we profiled the transcriptomes of ∼60,000 cells from four primary NPC and two rNPC cases to provide deeper insights into the dynamic changes in rNPC within radiation fields. Heterogeneity of both immune cells (T, natural killer, B, and myeloid cells) and tumor cells was characterized. Recurrent samples showed increased infiltration of regulatory T cells in a highly immunosuppressive state and CD8⁺ T cells in a highly cytotoxic and dysfunctional state. Enrichment of M2-polarized macrophages and LAMP3⁺ dendritic cells conferred enhanced immune suppression to rNPC. Furthermore, malignant cells showed enhanced immune-related features, such as antigen presentation. Elevated regulatory T cell levels were associated with a worse prognosis, with certain receptor-ligand communication pairs identified in rNPC. Even with relatively limited samples, our study provides important clues to complement the exploitation of rNPC immune environment and will help advance targeted immunotherapy of rNPC.

Keywords: Nasopharyngeal carcinoma; immune cells; recurrence; single-cell RNA sequencing; tumor microenvironment.

Publication types

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

MeSH terms

CD8-Positive T-Lymphocytes
Humans
Nasopharyngeal Carcinoma / genetics
Nasopharyngeal Carcinoma / pathology
Nasopharyngeal Neoplasms* / genetics
Nasopharyngeal Neoplasms* / pathology
Nasopharyngeal Neoplasms* / therapy
Neoplasm Recurrence, Local / genetics
Sequence Analysis, RNA
Tumor Microenvironment / genetics

Grants and funding

The study was supported by the National Key Technologies Research and Development Program on Prevention and Control of Chronic Noncommunicable Diseases (Grant No. 2018YFC1313204).