Oncogenic Mutations and Tumor Microenvironment Alterations of Older Patients With Diffuse Large B-Cell Lymphoma.

Abstract

The incidence of diffuse large B-cell lymphoma (DLBCL) increases by age and older DLBCL are commonly related to poor prognosis. However, the clinical and biological features of older DLBCL patients remain to be determined. A total of 2,445 patients with newly diagnosed DLBCL were enrolled for clinical data analysis according to age at diagnosis, with tumor samples of 1,150 patients assessed by DNA sequencing and 385 patients by RNA sequencing. Older DLBCL presented advanced disease stage, elevated serum lactate dehydrogenase, poor performance status, multiple extranodal involvement, high percentage of double expressor subtype, and adverse clinical outcome. According to molecular features, age was positively correlated with the oncogenic mutations of PIM1, MYD88, BTG2, CD79B, TET2, BTG1, CREBBP, TBL1XR1, and with the MYD88-like genetic subtype. These oncogenic mutations were involved in B-cell receptor/NF-κB signaling, B-cell differentiation, and histone acetylation based on biological functions. Older DLBCL also manifested reduction in CD4+ naïve T and CD8+ naïve T cells, and also increased recruitment of exhausted T cells and macrophages, leading to immunosuppressive tumor microenvironment. Our work thus contributes to the understanding of aging-related oncogenic mutations and tumor microenvironment alterations in lymphoma progression, and may provide new insights to mechanism-based targeted therapy in DLBCL.

• Authors: Yue Zhu, Di Fu, Qing Shi, Ziyang Shi, Lei Dong, Hongmei Yi, Zhenhua Liu, Yan Feng, Qian Liu, Hai Fang, Shu Cheng, Li Wang, Qiang Tian, Pengpeng Xu, Weili Zhao
• Journal: Frontiers in immunology (Front Immunol) Vol. 13 Pg. 842439 ( 2022) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 35401516 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Zhu, Fu, Shi, Shi, Dong, Yi, Liu, Feng, Liu, Fang, Cheng, Wang, Tian, Xu and Zhao.

Chemical References

• Immediate-Early Proteins
• Myeloid Differentiation Factor 88
• Tumor Suppressor Proteins
• BTG2 protein, human

Topics

• Humans
• Immediate-Early Proteins (genetics)
• Lymphoma, Large B-Cell, Diffuse (pathology)
• Mutation
• Myeloid Differentiation Factor 88 (metabolism)
• Tumor Microenvironment (genetics)
• Tumor Suppressor Proteins (genetics)
• Exome Sequencing