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KMID : 1142020220570020117
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Blood Research
2022 Volume.57 No. 2 p.117 ~ p.128
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Diffuse large B-cell lymphoma (DLBCL) is infiltrated with activated CD8+ T-cells despite immune checkpoint signaling
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Greenbaum Adam M.
Fromm Jonathan R.
Gopal Ajay K.
Houghton A. McGarry
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Abstract
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Background: B-cell non-Hodgkin lymphomas (NHL) are hematologic malignancies that arise in the lymph node. Despite this, the malignant cells are not cleared by the immune cells present. The failure of anti-tumor immunity may be due to immune checkpoints such as the PD-1/PDL-1 axis, which can cause T-cell exhaustion. Unfortunately, unlike Hodgkin lymphoma, checkpoint blockade in NHL has shown limited efficacy.
Methods: We performed an extensive functional analysis of malignant and non-malignant lymph nodes using high dimensional flow cytometry. We compared follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and lymph nodes harboring reactive hyperplasia (RH).
Results: We identified an expansion of CD8+PD1+ T-cells in the lymphomas relative to RH. Moreover, we demonstrate that these cells represent a mixture of activated and exhausted T-cells in FL. In contrast, these cells are nearly universally activated and functional in DLBCL. This is despite expression of counter-regulatory molecules such as PD-1, TIM-3, and CTLA-4, and the presence of regulatory T-cells.
Conclusions: These data may explain the failure of single-agent immune checkpoint inhibitors in the treatment of DLBCL. Accordingly, functional differences of CD8+ T-cells between FL and DLBCL may inform future therapeutic targeting strategies.
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KEYWORD
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Lymphoma, immune microenvironment, Immune checkpoint inhibition
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