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Original Article | Open Access

Single-cell RNA-seq reveals the immune escape and drug resistance mechanisms of mantle cell lymphoma

Liang Wang1,2 ( ), Steven Mo3, Xin Li1, Yingzhi He4, Jing Yang1
Department of Hematology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University and Capital Medical University, Beijing Tongren Hospital, Beijing 100730, China
Nanning Life-Ontology Biotechnology Co., Ltd., Nanning 530000, China
Department of Hematology, Zhujiang Hospital of Southern Medical University, Guangzhou 510280, China
Show Author Information

Abstract

Objective

Mantle cell lymphoma (MCL) is a rare subtype of non-Hodgkin lymphoma (NHL) with high heterogeneity and a high recurrence rate. How heterogenous cell populations contribute to relapse remains to be elucidated.

Methods

We performed single cell RNA sequencing (scRNA-seq) on approximately 4,000 bone marrow cells sampled from one patient with multidrug resistant MCL. We identified 10 subpopulations comprising 4 malignant B cell subtypes, 3 T cell subtypes, 2 dendritic cell subtypes and 1 natural killer (NK) cell subtype. Subsequently, we identified cell markers, including a series of genes associated with immune escape and drug resistance. In addition, we explored the roles of these genes in the mechanism of immune escape and drug resistance, and we verified the expression imbalance and clinical prognostic potential by using GEO datasets including 211 MCL samples.

Results

The major immune escape mechanisms of MCL included anti-perforin activity, decreased immunogenicity and direct inhibition of apoptosis and cell killing, as mediated by type Ⅰ and Ⅱ B cells. The drug resistance mechanisms of different cell clusters included drug metabolism, DNA damage repair, apoptosis and survival promotion. Type Ⅲ B cells closely communicate with other cells. The key genes involved in the resistance mechanisms showed dysregulated expression and may have significant clinical prognostic value.

Conclusion

This study investigated potential immune escape and drug resistance mechanisms in MCL. The results may guide individualized treatment and promote the development of therapeutic drugs.

Keywords

multidrug resistancemantle cell lymphomascRNA-seqimmune escapeCell heterogeneity

Electronic Supplementary Material

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Cancer Biology & Medicine
Volume 17 Issue 3,
August 2020
Pages 726-739
DOI: 10.20892/j.issn.2095-3941.2020.0073
Cite this article:
Wang L, Mo S, Li X, et al. Single-cell RNA-seq reveals the immune escape and drug resistance mechanisms of mantle cell lymphoma. Cancer Biology & Medicine, 2020, 17(3): 726-739. https://doi.org/10.20892/j.issn.2095-3941.2020.0073

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Received: 21 February 2020
Accepted: 28 April 2020
Published: 15 August 2020
©2020 Cancer Biology & Medicine.

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