PD‑1 blockade enhances cytokine‑induced killer cell‑mediated cytotoxicity in B‑cell non‑Hodgkin lymphoma cell lines

Li,Yutao; Sharma,Amit; Bloemendal,Maurits W.J.R.; Schmidt‑Wolf,Roland; Kornek,Miroslaw; Schmidt‑Wolf,Ingo G.H.

doi:10.3892/ol.2021.12874

August-2021 Volume 22 Issue 2

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August-2021 Volume 22 Issue 2

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Article Open Access

PD‑1 blockade enhances cytokine‑induced killer cell‑mediated cytotoxicity in B‑cell non‑Hodgkin lymphoma cell lines

Authors:
- Yutao Li
- Amit Sharma
- Maurits W.J.R. Bloemendal
- Roland Schmidt‑Wolf
- Miroslaw Kornek
- Ingo G.H. Schmidt‑Wolf
View Affiliations / Copyright

Affiliations: Department of Integrated Oncology (CIO), University Hospital Bonn, D‑53127 Bonn, Germany, Department of Biosciences, Hogeschool van Arnhem en Nijmegen University of Applied Sciences, 6525EM Nijmegen, The Netherlands, Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, D‑53127 Bonn, Germany, Department of Medicine I, University Hospital Bonn, D‑53127 Bonn, Germany

Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Article Number: 613
|
Published online on: June 23, 2021

https://doi.org/10.3892/ol.2021.12874
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Abstract

The clinical utility of immune checkpoint inhibitors, such as programmed cell death protein 1 (PD‑1) and programmed death‑ligand 1 (PD‑L1) inhibitors used alone or in combination with other therapies, is currently gaining attention. In this particular scenario, the inclusion of cytokine‑induced killer (CIK) cells has proven to be a novel therapeutic approach. CIK cells have shown anticancer activity in various hematopoietic malignancies, but their defined cytotoxicity in B‑cell non‑Hodgkin lymphoma (B‑NHL) remains to be fully elucidated. The present study investigated the role of PD‑1/PD‑L1 blockades on the cytotoxic efficacy of CIK cells primarily in B‑NHL cell lines. The current analysis revealed that CIK cells prompted cytotoxicity against B‑NHL cell lines (DAUDI and SU‑DHL‑4), and a significant increase in PD‑L1 expression was observed when CIK cells were co‑cultured with B‑NHL cells. Additionally, a combination of PD‑1 and PD‑L1 antibodies with CIK cells significantly decreased cell viability only in DAUDI cells. Furthermore, IFN‑γ elevation was observed in both cell lines treated with CIK alone or with PD‑1 antibody, but this tendency was not observed for PD‑L1. Since PD‑1 can suppress immune inactivation, whereas CD40L can promote it, the effects of CD40L blockade were also examined; however, no significant changes in cell viability were observed. Overall, the present in vitro data suggested that CIK cells exerted a cytotoxic function in B‑NHL cells, and a combination of PD‑1 inhibitors with CIK cells may provide a potential therapeutic option for this type of lymphoma. Nevertheless, in vivo experiments are warranted to undermine the extent to which PD‑1 inhibitors may be used to enhance the antitumor activity of CIK cells in B‑NHL.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

PD‑1 blockade enhances cytokine‑induced killer cell‑mediated cytotoxicity in B‑cell non‑Hodgkin lymphoma cell lines

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