Dendritic Cell-Based Immunotherapy for Myeloid Leukemias

Schürch, Christian M.; Riether, Carsten; Ochsenbein, Adrian F. (2013). Dendritic Cell-Based Immunotherapy for Myeloid Leukemias. Frontiers in immunology, 4(496), p. 496. Frontiers Research Foundation 10.3389/fimmu.2013.00496

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Acute and chronic myeloid leukemia (AML, CML) are hematologic malignancies arising from oncogene-transformed hematopoietic stem/progenitor cells known as leukemia stem cells (LSCs). LSCs are selectively resistant to various forms of therapy including irradiation or cytotoxic drugs. The introduction of tyrosine kinase inhibitors has dramatically improved disease outcome in patients with CML. For AML, however, prognosis is still quite dismal. Standard treatments have been established more than 20 years ago with only limited advances ever since. Durable remission is achieved in less than 30% of patients. Minimal residual disease (MRD), reflected by the persistence of LSCs below the detection limit by conventional methods, causes a high rate of disease relapses. Therefore, the ultimate goal in the treatment of myeloid leukemia must be the eradication of LSCs. Active immunotherapy, aiming at the generation of leukemia-specific cytotoxic T cells (CTLs), may represent a powerful approach to target LSCs in the MRD situation. To fully activate CTLs, leukemia antigens have to be successfully captured, processed, and presented by mature dendritic cells (DCs). Myeloid progenitors are a prominent source of DCs under homeostatic conditions, and it is now well established that LSCs and leukemic blasts can give rise to "malignant" DCs. These leukemia-derived DCs can express leukemia antigens and may either induce anti-leukemic T cell responses or favor tolerance to the leukemia, depending on co-stimulatory or -inhibitory molecules and cytokines. This review will concentrate on the role of DCs in myeloid leukemia immunotherapy with a special focus on their generation, application, and function and how they could be improved in order to generate highly effective and specific anti-leukemic CTL responses. In addition, we discuss how DC-based immunotherapy may be successfully integrated into current treatment strategies to promote remission and potentially cure myeloid leukemias.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology > Autopsy
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology

UniBE Contributor:

Schürch, Christian; Riether, Carsten and Ochsenbein, Adrian

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

1664-3224

Publisher:

Frontiers Research Foundation

Language:

English

Submitter:

Marianne Zahn

Date Deposited:

28 Mar 2014 09:17

Last Modified:

12 Mar 2021 15:29

Publisher DOI:

10.3389/fimmu.2013.00496

PubMed ID:

24427158

Uncontrolled Keywords:

active, dendritic cells, immunotherapy, leukemia stem cells, minimal residual disease, myeloid leukemia

BORIS DOI:

10.7892/boris.45040

URI:

https://boris.unibe.ch/id/eprint/45040

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