Tumor evolution and immune microenvironment dynamics in primary and relapsed mantle cell lymphoma
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
- Rong Fan (ORCID: https://orcid.org/0000-0001-7805-8059)
- Man Nie (ORCID: https://orcid.org/0000-0001-6109-9268)
- Zhiliang Bai (ORCID: https://orcid.org/0000-0002-3977-3057)
- Hui Wan (ORCID: https://orcid.org/0000-0002-4368-8672)
- Kui Wu (ORCID: https://orcid.org/0000-0002-6857-7231)
- Ming‐Yu Yang (ORCID: https://orcid.org/0000-0002-6841-5478)
- Rose‐Marie Amini (ORCID: https://orcid.org/0000-0003-0901-5252)
- Dongbing Liu (ORCID: https://orcid.org/0000-0003-2870-5187)
- Leire de Campos‐Mata (ORCID: https://orcid.org/0000-0003-1998-4014)
- Archibald Enninful (ORCID: https://orcid.org/0000-0002-6350-6530)
- Likun Du (ORCID: https://orcid.org/0000-0002-8448-2187)
- Mirjam van der Burg (ORCID: https://orcid.org/0000-0002-1510-3104)
- Birgitta Sander (ORCID: https://orcid.org/0000-0002-1214-1340)
- Weicheng Ren (ORCID: https://orcid.org/0000-0002-7874-825X)
- Mattias Berglund (ORCID: https://orcid.org/0000-0002-0128-7635)
- Stephen M. Ansell (ORCID: https://orcid.org/0000-0003-1244-6758)
- Agata M. Wasik (ORCID: https://orcid.org/0000-0002-5020-3856)
- Qiang Pan‐Hammarström (ORCID: https://orcid.org/0000-0003-1990-8804)
- Rui Sun (ORCID: https://orcid.org/0000-0002-5616-6849)
- Xiaobo Li (ORCID: https://orcid.org/0000-0003-1040-2022)
- Yating Wang (ORCID: https://orcid.org/0000-0002-5057-4083)
- Chunli Yang (ORCID: https://orcid.org/0000-0003-0298-2266)
- Xiaofei Ye (ORCID: https://orcid.org/0000-0002-7678-1152)
- Zhi-Zhang Yang
Institutions
- BGI Group (China) (CN)
- Uppsala University (SE)
- Karolinska University Hospital (SE)
- Sun Yat-sen University (CN)
- Karolinska Institutet (SE)
- Yale University (US)
- Mayo Clinic in Arizona (US)
- Sun Yat-sen University Cancer Center (CN)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2025-08-27
- DOI
- https://doi.org/10.1016/j.xcrm.2025.102318
- Citations
- 4
- Primary Topic
- Lymphoma Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 5.89
Funders
- Cancerfonden
- Karolinska Institutet
- Knut och Alice Wallenbergs Stiftelse
- Vetenskapsrådet
- Radiumhemmets Forskningsfonder
- O. E. och Edla Johanssons Vetenskapliga Stiftelse