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Clinical significance of T-cell exhaustion in patients with diffuse large B-cell lymphoma

Hematological Oncology Jun 19, 2019

Leppä S, et al. - Researchers sought to describe the immunological profiles of diffuse large B-cell lymphoma (DLBCL) via multiplex immunohistochemistry (mIHC) with digital image analysis and associated the findings with the outcome. Utilizing the NanoString platform with a 770-gene PanCancer Immune panel, they conducted gene expression analysis for 81 DLBCL samples. The DLBCL samples showed a high degree of heterogeneity in transcriptome level. Gene expression signatures with highly correlating genes were identified in correlation matrix analysis. Genes for cytolytic factors and immune checkpoint molecules (GZMB, PRF1, IFNG, TIM3, LAG3) and T-cells (CD3, CD2, CD28), together entitled as a T-cell signature, macrophages (CD68, CD163), B-cells (MS4A1, CD19, CD79A/B), and extracellular matrix (FN1, ITGA1/5/6, VEGFA) were contained in the main signatures. Survival was not identified to be correlated with any of the gene expression signatures. Patients with DLBCL showed unfavorable survival in correlation to putative markers of T-cell exhaustion. An independent cohort of 137 DLBCL patients treated with immunochemotherapy validated the adverse prognostic impact of exhausted T-cells on survival.
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