Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Cyclophosphamide induces dynamic alterations in the host microenvironments resulting in a Flt3 ligand-dependent expansion of dendritic cells
Journal of Immunology, Volume 184, No. 4, Year 2010
Notification
URL copied to clipboard!
Description
Preconditioning a recipient host with lymphodepletion can markedly augment adoptive T cell therapy. However, the precise mechanisms involved are poorly understood. In a recent study, we observed a significant increase in the circulating levels of dendritic cells (DCs; CD11c+CD11b+) during the recovery from cyclophosphamide (CTX)-induced lymphodepletion. Herein, we demonstrate that the CTX-induced DC expansion was not altered by adjuvant chemotherapy or tumor burden but was augmented by coadministration of granulocyte-colony stimulating factor. Although the increase in the number of DCs was preceded by a systemic expansion of a population expressing the phenotype of myeloid-derived suppressor cells (Gr-1+CD11b +), depletion of these Gr-1+ cells had no effect on the noted expansion. Moreover, when Gr-1highCD11bhigh cells were sorted from CTX-treated mice and adoptively transferred into control or CTX-treated recipients, they did not differentiate into DCs. Post-CTX expansion of DCs was associated with proliferation of DCs in bone marrow (BM) during the lymphopenic phase and in the blood and spleen during the recovery phase. Furthermore, adoptive transfer of BM cells from CTX-treated mice produced equal numbers of DCsin the blood of either CTX-treated or untreated recipients. CTX induced a dynamic surge in the expression of growth factors and chemokines in BM, where CCR2 and Flt3 signaling pathways were critical for DC expansion. In sum, our data suggest that CTX induces proliferation of DCs in BM prior to their expansion in the periphery. Targeting DCs at these phases would significantly improve their contribution to the clinical application of lymphodepletion to adoptive immunotherapy. Copyright © 2010 by The American Association of Immunologists, Inc.
Authors & Co-Authors
Salem, Mohamed Labib
United States, Charleston
Medical University of South Carolina
Al-Khami, Amir A.
Egypt, Tanta
Faculty of Science
El Naggar, Sabry Ali
Egypt, Tanta
Faculty of Science
Díaz-Montero, Claudia Marcela
United States, Miami
Sylvester Comprehensive Cancer Center
Chen, Yian
United States, Charleston
Medical University of South Carolina
Cole, David J.
United States, Charleston
Medical University of South Carolina
Statistics
Citations: 68
Authors: 6
Affiliations: 3
Identifiers
Doi:
10.4049/jimmunol.0902309
ISSN:
00221767
e-ISSN:
15506606
Research Areas
Cancer
Study Design
Cross Sectional Study