Next Article in Journal
Extracellular Vesicles and Cancer: A Focus on Metabolism, Cytokines, and Immunity
Previous Article in Journal
ESC, ALK, HOT and LOT: Three Letter Acronyms of Emerging Renal Entities Knocking on the Door of the WHO Classification
Previous Article in Special Issue
In the Absence of a TCR Signal IL-2/IL-12/18-Stimulated γδ T Cells Demonstrate Potent Anti-Tumoral Function Through Direct Killing and Senescence Induction in Cancer Cells
Open AccessArticle

Differential Depletion of Bone Marrow Resident B-ALL after Systemic Administration of Endosomal TLR Agonists

1
Michael Cuccione Childhood Cancer Research Program, BC Children’s Hospital Research Institute, Vancouver, BC V5Z 4H4, Canada
2
Department of Pathology, School of Medicine, Stanford University, Stanford, CA 94305, USA
3
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
4
Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
5
Department of Pediatrics, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(1), 169; https://doi.org/10.3390/cancers12010169
Received: 19 December 2019 / Revised: 4 January 2020 / Accepted: 8 January 2020 / Published: 10 January 2020
(This article belongs to the Special Issue Targeting Innate Immunity Cells in Cancer)
Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. While frontline chemotherapy regimens are generally very effective, the prognosis for patients whose leukemia returns remains poor. The presence of measurable residual disease (MRD) in bone marrow at the completion of induction therapy is the strongest predictor of relapse, suggesting that strategies to eliminate the residual leukemic blasts from this niche could reduce the incidence of recurrence. We have previously reported that toll-like receptor (TLR) agonists achieve durable T cell-mediated protection in transplantable cell line-based models of B cell precursor leukemia (B-ALL). However, the successful application of TLR agonist therapy in an MRD setting would require the induction of anti-leukemic immune activity specifically in the bone marrow, a site of the chemotherapy-resistant leukemic blasts. In this study, we compare the organ-specific depletion of human and mouse primary B-ALL cells after systemic administration of endosomal TLR agonists. Despite comparable splenic responses, only the TLR9 agonist induced strong innate immune responses in the bone marrow and achieved a near-complete elimination of B-ALL cells. This pattern of response was associated with the most significantly prolonged disease-free survival. Overall, our findings identify innate immune activity in the bone marrow that is associated with durable TLR-induced protection against B-ALL outgrowth. View Full-Text
Keywords: acute lymphoblastic leukemia; minimal residual disease; bone marrow; toll-like receptor; innate immunity; immunotherapy acute lymphoblastic leukemia; minimal residual disease; bone marrow; toll-like receptor; innate immunity; immunotherapy
Show Figures

Figure 1

MDPI and ACS Style

Jo, S.; Fotovati, A.; Duque-Afonso, J.; Cleary, M.L.; van den Elzen, P.; Seif, A.E.; Reid, G.S. Differential Depletion of Bone Marrow Resident B-ALL after Systemic Administration of Endosomal TLR Agonists. Cancers 2020, 12, 169.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop