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Article

Dendritic Cell-Triggered Immune Activation Goes along with Provision of (Leukemia-Specific) Integrin Beta 7-Expressing Immune Cells and Improved Antileukemic Processes

by
Elias Rackl
1,
Lin Li
1,
Lara Kristina Klauer
1,
Selda Ugur
1,
Elena Pepeldjiyska
1,
Corinna L. Seidel
2,
Carina Gunsilius
1,
Melanie Weinmann
1,
Fatemeh Doraneh-Gard
1,
Nina Reiter
1,
Caroline Plett
1,
Daniel Christoph Amberger
1,
Peter Bojko
3,
Doris Kraemer
4,
Jörg Schmohl
5,
Andreas Rank
6,
Christoph Schmid
6 and
Helga Maria Schmetzer
1,*
1
Department of Medicine III, University Hospital of Munich, 81377 Munich, Germany
2
Department of Orthodontics and Dentofacial Orthopedics, University Hospital, LMU Munich, 80336 Munich, Germany
3
Department of Hematology and Oncology, Rotkreuzklinikum Munich, 80634 Munich, Germany
4
Department of Hematology and Oncology, St.-Josefs-Hospital, 58097 Hagen, Germany
5
Department of Hematology and Oncology, Diakonieklinikum Stuttgart, 70176 Stuttgart, Germany
6
Department of Hematology and Oncology, University Hospital of Augsburg, 86156 Augsburg, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2023, 24(1), 463; https://doi.org/10.3390/ijms24010463
Submission received: 4 July 2022 / Revised: 19 December 2022 / Accepted: 21 December 2022 / Published: 27 December 2022
(This article belongs to the Special Issue Dendritic Cell and Cancer Therapy)
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Abstract

Integrin beta 7 (β7), a subunit of the integrin receptor, is expressed on the surface of immune cells and mediates cell–cell adhesions and interactions, e.g., antitumor or autoimmune reactions. Here, we analyzed, whether the stimulation of immune cells by dendritic cells (of leukemic derivation in AML patients or of monocyte derivation in healthy donors) leads to increased/leukemia-specific β7 expression in immune cells after T-cell-enriched mixed lymphocyte culture—finally leading to improved antileukemic cytotoxicity. Healthy, as well as AML and MDS patients’ whole blood (WB) was treated with Kit-M (granulocyte–macrophage colony-stimulating factor (GM-CSF) + prostaglandin E1 (PGE1)) or Kit-I (GM-CSF + Picibanil) in order to generate DCs (DCleu or monocyte-derived DC), which were then used as stimulator cells in MLC. To quantify antigen/leukemia-specific/antileukemic functionality, a degranulation assay (DEG), an intracellular cytokine assay (INTCYT) and a cytotoxicity fluorolysis assay (CTX) were used. (Leukemia-specific) cell subtypes were quantified via flow cytometry. The Kit treatment of WB (compared to the control) resulted in the generation of DC/DCleu, which induced increased activation of innate and adaptive cells after MLC. Kit-pretreated WB (vs. the control) led to significantly increased frequencies of β7-expressing T-cells, degranulating and intracellular cytokine-producing β7-expressing immune cells and, in patients’ samples, increased blast lysis. Positive correlations were found between the Kit-M-mediated improvement of blast lysis (vs. the control) and frequencies of β7-expressing T-cells. Our findings indicate that DC-based immune therapies might be able to specifically activate the immune system against blasts going along with increased frequencies of (leukemia-specific) β7-expressing immune cells. Furthermore, β7 might qualify as a predictor for the efficiency and the success of AML and/or MDS therapies.
Keywords: integrin beta 7; leukemia-derived dendritic cells; immune therapy; AML; MDS integrin beta 7; leukemia-derived dendritic cells; immune therapy; AML; MDS

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MDPI and ACS Style

Rackl, E.; Li, L.; Klauer, L.K.; Ugur, S.; Pepeldjiyska, E.; Seidel, C.L.; Gunsilius, C.; Weinmann, M.; Doraneh-Gard, F.; Reiter, N.; et al. Dendritic Cell-Triggered Immune Activation Goes along with Provision of (Leukemia-Specific) Integrin Beta 7-Expressing Immune Cells and Improved Antileukemic Processes. Int. J. Mol. Sci. 2023, 24, 463. https://doi.org/10.3390/ijms24010463

AMA Style

Rackl E, Li L, Klauer LK, Ugur S, Pepeldjiyska E, Seidel CL, Gunsilius C, Weinmann M, Doraneh-Gard F, Reiter N, et al. Dendritic Cell-Triggered Immune Activation Goes along with Provision of (Leukemia-Specific) Integrin Beta 7-Expressing Immune Cells and Improved Antileukemic Processes. International Journal of Molecular Sciences. 2023; 24(1):463. https://doi.org/10.3390/ijms24010463

Chicago/Turabian Style

Rackl, Elias, Lin Li, Lara Kristina Klauer, Selda Ugur, Elena Pepeldjiyska, Corinna L. Seidel, Carina Gunsilius, Melanie Weinmann, Fatemeh Doraneh-Gard, Nina Reiter, and et al. 2023. "Dendritic Cell-Triggered Immune Activation Goes along with Provision of (Leukemia-Specific) Integrin Beta 7-Expressing Immune Cells and Improved Antileukemic Processes" International Journal of Molecular Sciences 24, no. 1: 463. https://doi.org/10.3390/ijms24010463

APA Style

Rackl, E., Li, L., Klauer, L. K., Ugur, S., Pepeldjiyska, E., Seidel, C. L., Gunsilius, C., Weinmann, M., Doraneh-Gard, F., Reiter, N., Plett, C., Amberger, D. C., Bojko, P., Kraemer, D., Schmohl, J., Rank, A., Schmid, C., & Schmetzer, H. M. (2023). Dendritic Cell-Triggered Immune Activation Goes along with Provision of (Leukemia-Specific) Integrin Beta 7-Expressing Immune Cells and Improved Antileukemic Processes. International Journal of Molecular Sciences, 24(1), 463. https://doi.org/10.3390/ijms24010463

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