AUTHOR=Mu Shidai , Shi Deyao , Ai Lisha , Fan Fengjuan , Peng Fei , Sun Chunyan , Hu Yu 

TITLE=International Prognostic Index-Based Immune Prognostic Model for Diffuse Large B-Cell Lymphoma

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.732006

DOI=10.3389/fimmu.2021.732006

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>The International Prognostic Index (IPI) is widely used to discriminate the prognosis of patients with diffuse large B-cell lymphoma (DLBCL). However, there is a significant need to identify novel valuable biomarkers in the context of targeted therapy, such as immune checkpoint blockade (ICB).</p></sec><sec><title>Methods</title><p>Gene expression data and clinical DLBCL information were obtained from The Cancer Genome Atlas and Gene Expression Omnibus datasets. A total of 371 immune-related genes in DLBCL patients associated with different IPI risk groups were identified by weighted gene co-expression network analysis, and eight genes were selected to construct an IPI-based immune prognostic model (IPI-IPM). Subsequently, we analyzed the somatic mutation and transcription profiles of the IPI-IPM subgroups as well as the potential clinical response to immune checkpoint blockade (ICB) in IPI-IPM subgroups.</p></sec><sec><title>Results</title><p>The IPI-IPM was constructed based on the expression of <italic>CMBL</italic>, <italic>TLCD3B</italic>, <italic>SYNDIG1</italic>, <italic>ESM1</italic>, <italic>EPHA3</italic>, <italic>HUNK</italic>, <italic>PTX3</italic>, and <italic>IL12A</italic>, where high-risk patients had worse overall survival than low-risk patients, consistent with the results in the independent validation cohorts. The comprehensive results showed that high IPI-IPM risk scores were correlated with immune-related signaling pathways, high <italic>KMT2D</italic> and <italic>CD79B</italic> mutation rates, and upregulation of inhibitory immune checkpoints, including <italic>PD-L1</italic>, <italic>BTLA</italic>, and <italic>SIGLEC7</italic>, indicating a greater potential response to ICB therapy.</p></sec><sec><title>Conclusion</title><p>The IPI-IPM has independent prognostic significance for DLBCL patients, which provides an immunological perspective to elucidate the mechanisms of tumor progression and sheds light on the development of immunotherapy for DLBCL.</p></sec>