Tumor evolution and immune microenvironment dynamics in primary and relapsed mantle cell lymphoma.

Wan H, Ren W, Yang M, Nie M, Wasik AM, Du L, de Campos-Mata L, Sun R, Bai Z, Enninful A, Wang Y, Berglund M, Amini RM, Li X, Yang C, Ye X, Yang ZZ, Ansell SM, Liu D, van der Burg M, Fan R, Wu K, Sander B, Pan-Hammarström Q

Cell Reports Medicine 6 (9) 102318 [2025-09-16; online 2025-08-27]

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.

Bioinformatics Support for Computational Resources [Service]

PubMed 40876452

DOI 10.1016/j.xcrm.2025.102318

Crossref 10.1016/j.xcrm.2025.102318

pmc: PMC12490240
pii: S2666-3791(25)00391-X