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Digital spatial profiling uncovers transcriptomic features of distinct plasma cell-like phenotypes in diffuse large
Zucheng Xie1, Yan Qin2, Xuemin Xue3
1Department of Medical Oncology, Beijing Key Laboratory of Key Technologies for Early Clinical Trial Evaluation of Innovative Drugs for Major Diseases, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Blood Advances
|March 26, 2026
Summary
Diffuse large B-cell lymphoma (DLBCL) has diverse plasma cell-like phenotypes. Identifying these phenotypes offers new prognostic insights and potential for personalized treatment strategies in DLBCL.
Area of Science:
- Hematology
- Oncology
- Genomics
Background:
- Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous malignancy with complex treatment and prognostic challenges.
- The prognostic and therapeutic implications of plasma cell-like phenotypes within DLBCL are not well understood.
Purpose of the Study:
- To characterize distinct plasma cell-like phenotypes in DLBCL using spatially-resolved transcriptomics.
- To investigate the prognostic relevance and therapeutic implications of these phenotypes.
Main Methods:
- Spatially-resolved transcriptomics was employed to profile four phenotypes in DLBCL based on CD20, HLA-DRA, and PRDM1 expression.
- Patients were classified as DLBCL plasma cell-like phenotype predominant (DLBCLPCPP) or deficient (DLBCLPCPD) based on the percentage of plasma cell-like cells.
- A random forest model was developed to predict bortezomib response using plasma cell-like phenotype-associated genes.
Main Results:
- Three plasma cell-like phenotypes were associated with worse prognosis, while one non-plasma cell-like phenotype correlated with better prognosis.
- DLBCLPCPP showed a higher rate of disease progression and increased B2M alterations compared to DLBCLPCPD.
- Plasma cell-like phenotypes were linked to reduced proliferation, impaired immune function, and altered tumor microenvironment.
- High plasma cell-like phenotype signatures predicted poorer progression-free survival (PFS) but greater benefit from R-CHOP plus bortezomib.
Conclusions:
- Distinct plasma cell-like phenotypes in DLBCL have significant prognostic implications.
- These findings highlight the potential for individualized treatment strategies, including the use of bortezomib in specific patient subgroups.
- Further research into these phenotypes may improve DLBCL management and patient outcomes.
