Tumor evolution and immune microenvironment dynamics in primary and relapsed mantle cell lymphoma
Cell Reports Medicine, vol. 6, pp. 102318
Abstract
Mantle cell lymphoma (MCL) is a rare but often aggressive type of B cell lymphoma with a high risk of relapse. To explore intratumoral clonal diversity and tumor evolution related to disease relapse, we integrate single-cell RNA and B cell receptor sequencing with whole-genome sequencing in 20 diagnosed/untreated and/or relapsed samples from 11 MCL patients. Our results reveal significant intratumor heterogeneity in MCL already at diagnosis. We further show that the evolutionary paths during disease progression for each patient are unique, where minor clones present at diagnosis may acquire different mutations and copy-number variations and/or migrate to various microenvironments. Despite significant interpatient heterogeneity, recurrent genetic and transcriptomic changes in tumor cells affecting key signaling pathways, along with alterations involved in the tumor microenvironment, are also observed during disease progression. Taken together, our findings elucidate the diverse and dynamic tumor-immune evolution processes associated with disease progression and relapse in MCL.
Authors 24
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Affiliation as printed
Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
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Affiliation as printed
Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
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BGI Group (China) · Karolinska Institutet · BGI Research
Affiliation as printed
Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden; Guangdong Provincial Key Laboratory of Human Disease Genomic, Shenzhen Key Laboratory of Genomics, BGI Research, Shenzhen, China
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Sun Yat-sen University · Sun Yat-sen University Cancer Center · State Key Laboratory of Oncology in South China
Affiliation as printed
Department of Medical Oncology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
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Karolinska University Hospital · Karolinska Institutet
Affiliation as printed
Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
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Affiliation as printed
Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
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Affiliation as printed
Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
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Affiliation as printed
Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
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Affiliation as printed
Department of Biomedical Engineering, Yale University, New Haven, CT, USA
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Affiliation as printed
Department of Biomedical Engineering, Yale University, New Haven, CT, USA
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Affiliation as printed
Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
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Affiliation as printed
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
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Affiliation as printed
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
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Affiliation as printed
Guangdong Provincial Key Laboratory of Human Disease Genomic, Shenzhen Key Laboratory of Genomics, BGI Research, Shenzhen, China
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Sichuan University · West China Hospital of Sichuan University · State Key Laboratory of Biotherapy
Affiliation as printed
Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China; Department of Medical Oncology, West China Hospital, Sichuan University, Chengdu, China
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Affiliation as printed
Kindstar Global Precision Medicine Institute, Wuhan, China
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Affiliation as printed
Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, MN, USA
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Affiliation as printed
Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, MN, USA
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BGI Group (China) · BGI Genomics · BGI Research
Affiliation as printed
Guangdong Provincial Key Laboratory of Human Disease Genomic, Shenzhen Key Laboratory of Genomics, BGI Research, Shenzhen, China; BGI Genomics, Shenzhen, China
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Mirjam van der Burg Aachen Laboratory for Pediatric Immunology Department of Pediatrics, Willem-Alexander Children's Hospital
Leiden University Medical Center · Willem-Alexander Kinderziekenhuis
Affiliation as printed
Laboratory for Pediatric Immunology, Department of Pediatrics, Willem Alexander Children's Hospital, Leiden University Medical Center, Leiden, the Netherlands
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Affiliation as printed
Department of Biomedical Engineering, Yale University, New Haven, CT, USA
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Kui Wu corresponding
BGI Group (China) · BGI Genomics · BGI Research
Affiliation as printed
Guangdong Provincial Key Laboratory of Human Disease Genomic, Shenzhen Key Laboratory of Genomics, BGI Research, Shenzhen, China; BGI Genomics, Shenzhen, China. Electronic address: wukui@genomics.cn
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Birgitta Sander corresponding
Karolinska University Hospital · Karolinska Institutet
Affiliation as printed
Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden. Electronic address: birgitta.sander@ki.se
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Qiang Pan‐Hammarström corresponding
Affiliation as printed
Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden. Electronic address: qiang.pan-hammarstrom@ki.se
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