title: Effect of administration timing of postchemotherapy granulocyte colony-stimulating factor on host-immune cell recovery and CD8+T-cell response.
abstract: Granulocyte colony-stimulating factor (G-CSF), a hematopoietic growth factor, is a standard supportive therapy given during cancer treatment. It induces acceleration in neutrophil recovery through stimulation of mobilization of hematopoietic progenitors. Given that the latter is also induced by chemotherapy itself, the timing of administration of G-CSF postchemotherapy might impact the resultant overall effects. The present study aimed to determine the optimal timing of G-CSF postchemotherapy to exert its optimal effects on the immune cell recovery and its impact on antigen-specific CD8+T-cell response. B6 mice were treated once with cyclophosphamide (4 mg/mouse; CTX) and then daily with G-CSF (5 g/mouse) from Days 1-5, 2-5 or 5-9 post-CTX treatment. The total numbers of various immune cell types were analyzed on Days 7, 9 and 12 post-CTX treatment. To evaluate effects on CD8+T-cell response, a pmel-1 transgenic mouse model was used in combination with prime boost peptide vaccination therapy. The total number of white blood cells (WBC), neutrophils, monocytes, lymphocytes, granulocytes and dendritic cells (DC) were significantly increased after G-CSF treatment in particular when G-CSF was administered from Days 2-5 post-CTX treatment. Application of this timing of G-CSF and CTX treatment after adoptive transfer of T-cells followed by prime-boost vaccination with antigenic peptide did not block the expansion of the donor pmel-1 CD8+T-cells. In conclusion, adjusting the timing of treatment with G-CSF postchemotherapy can optimize its promoting effects on recovery of myeloid cells without altering the associated antigen-specific immunity.
authors.affiliation: a Immunology and Biotechnology Division, Zoology Department , Tanta University , Tanta , Egypt.|b Center of Excellence in Cancer Research, Tanta University , Tanta , Egypt.
authors.forename: Mohamed Labib
authors.initials: ML
authors.lastname: Salem
authors.affiliation: a Immunology and Biotechnology Division, Zoology Department , Tanta University , Tanta , Egypt.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Nassef
authors.affiliation: a Immunology and Biotechnology Division, Zoology Department , Tanta University , Tanta , Egypt.
authors.forename: Soha G R
authors.initials: SG
authors.lastname: Abdel Salam
authors.affiliation: b Center of Excellence in Cancer Research, Tanta University , Tanta , Egypt.
authors.forename: Abdelaziz
authors.initials: A
authors.lastname: Zidan
authors.affiliation: c Deanship of Scientific Research, King Saud University , Riyadh , Saudi Arabia.|d Food Science and Nutrition Department , National Research Center , Dokki , Cairo , Egypt.
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: Mahmoud
authors.affiliation: e Laboratory of Immunology and Molecular Biology, Zoology Department, Faculty of Science , Assiut University , Assiut , Egypt.
authors.forename: Gamal
authors.initials: G
authors.lastname: Badr
authors.affiliation: f Surgery Department and Hollings Cancer Center , Medical University of South Carolina , Charleston , SC , USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Rubinstein
authors.affiliation: f Surgery Department and Hollings Cancer Center , Medical University of South Carolina , Charleston , SC , USA.
authors.forename: David
authors.initials: D
authors.lastname: Cole
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D002478:Cells, Cultured; D002985:Clinical Protocols; D003520:Cyclophosphamide / Q000009:adverse effects* / Q000627:therapeutic use; D004358:Drug Therapy; D064420:Drug-Related Side Effects and Adverse Reactions / Q000517:prevention & control*; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009369:Neoplasms / Q000188:drug therapy*; D009504:Neutrophils / Q000502:physiology*
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide
keywords: Antigen-specific immunity; G-CSF; cyclophosphamide; postchemotherapy