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논문 기본 정보

자료유형
학술저널
저자정보
Adam M. Greenbaum (Clinical Research Division Fred Hutchinson Cancer Research Center Seattle WA USA) Jonathan R. Fromm (Department of Laboratory Medicine University of Washington Seattle WA USA) Ajay K. Gopal (Clinical Research Division Fred Hutchinson Cancer Research Center Seattle WA USA) A. McGarry Houghton (Division of Pulmonary and Critical Care Medicine University of Washington Seattle WA USA)
저널정보
대한혈액학회 Blood Research Blood Research Vol.57 No.2
발행연도
2022.6
수록면
117 - 128 (12page)
DOI
10.5045/br.2022.2021145

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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. Conclusion 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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