High percentages of peripheral blood T-cell activation in childhood Hodgkin's lymphoma are associated with inferior outcome

Abstract

The aims of this study were to investigate the activation of T lymphocytes in peripheral blood from children with Hodgkin's lymphoma (HL) and explore their roles for prognosis in HL. A cohort of 52 newly diagnosed children with HL during the past 10 years was enrolled for analysis in this study. Peripheral blood samples of the patients were acquired before treatment in our hospital, and T-cell subsets were detected by a four-color flow cytometer. CD4+ T cells and CD4+/CD8+ T-cell ratio decreased significantly in patients with HL vs. healthy controls. CD8+ T cells, CD3+CD4+HLA-DR+ T cells, and CD3+CD8+HLA-DR+ T cells increased markedly in patients with HL vs. healthy controls. Receiver-operating characteristic (ROC) curve analysis showed that CD3+CD4+HLA-DR+ T cells and CD3+CD8+HLA-DR+ T cells each distinguished the high-risk group from the low- and intermediate-risk group. The area under the ROC curve for predicting high-risk patients was 0.795 for CD3+CD4+HLA-DR+ T cell and 0.784 for CD3+CD8+HLA-DR+ T cell. A comparison of peripheral blood T-cell subsets that responded differently to therapy showed significantly higher percentages of CD3+CD4+HLA-DR+ T cells and CD3+CD8+HLA-DR+ T cells in patients who achieved complete remission compared to those who did not achieve complete remission. In addition, high percentages of both CD3+CD4+HLA-DR+ T cells and CD3+CD8+HLA-DR+ T cells were associated with inferior event-free survival. Peripheral immune status may be related to disease severity in HL. CD3+CD4+HLA-DR+ T cells and CD3+CD8+HLA-DR+ T cells may be a novel indicator for risk stratification of HL and may be an independent risk factor for inferior outcome in childhood HL.

Tumor microenvironment and CAR‐T cell immunotherapy in B‐cell lymphoma

“…The nonimmune microenvironment is mainly composed of stromal cells such as cancer-associated fibroblasts (CAFs), extracellular matrix (ECM), pericytes, mesenchymal stromal cells, and stromal cells. [40][41][42] (Table 1).…”

“…The immune microenvironment includes regulatory T cells (Tregs), tumor‐associated macrophages (TAMs), myeloid‐derived suppressor cells (MDSCs), tumor‐associated neutrophils (TANs), natural killer cells (NKs), dendritic cells (DCs), etc., which mediate immunosuppressive microenvironment and immune evasion. The nonimmune microenvironment is mainly composed of stromal cells such as cancer‐associated fibroblasts (CAFs), extracellular matrix (ECM), pericytes, mesenchymal stromal cells, and stromal cells 40–42 . (Table 1).…”

Peripheral blood CD3+HLADR+ cells and associated gut microbiome species predict response and overall survival to immune checkpoint blockade

“…CD3+HLADR+ cells are deemed as activated T lymphocytes, which are upregulated in autoimmune diseases ( 9 ) and HIV infection ( 10 ). In cancer patients they have had divergent results, with high CD3+HLADR+ levels being associated with shorter relapse-free survival in Hodgkin and non-Hodgkin lymphoma ( 11 , 12 ), but with better response to neoadjuvant therapy in breast cancer ( 13 ). Studies assessing HLA-DR expression on lymphocytes as a potential biomarker for ICI therapy are scarce and focus mainly on single tumor entities ( 14 ).…”