title: Generation of potent dendritic cells with improved migration ability through p-cofilin and sarco/endoplasmic reticulum Ca(2+) transport ATPase 2 regulation.
abstract: OBJECTIVE
  It is important to improve the migratory ability of dendritic cells (DCs) and to increase DC potency for successful DC-based cancer immunotherapy. The intracellular Ca(2+) signaling pathway has an important role on the regulation of DC migration. Our preliminary studies revealed that sarco/endoplasmic reticulum Ca(2+) transport ATPase 2 (SERCA2) expression was inversely related to DC migratory capacity, and the expression level of p-cofilin and SERCA2 on mature DCs showed a counter-trend.
  
  
  METHODS
  We selected the appropriate six maturation cocktails on the basis of the expression levels of SERCA2 and p-cofilin and investigated the functional characteristics and migratory capacity of mature DCs. Among the these six maturation cocktails, DCIFN-γ/IL-1β/Poly-I:C showed potent type 1 immune response with interleukin (IL)-12p70 production and strong Th1-polarization, and this DC elicited strong antigen-specific cytotoxic T-lymphocyte responses.
  
  
  RESULTS
  Interestingly, DCIFN-γ/IL-1β/Poly-I:C showed lower expression of SERCA2 and higher expression of p-cofilin compared with those matured with the use of other cocktails. In vitro migration assay showed that DCs matured with the use of this maturation cocktail had significantly increased migratory ability compared with αDC1s and other DCs.
  
  
  CONCLUSIONS
  Interferon-γ, IL-1β and Poly-I:C maturation cocktail may be used in the field of cancer immunotherapy to generate potent immune-stimulatory DCs with improved type 1 immune response and migration capacity.
authors.affiliation: Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea.
authors.forename: Nu-Ri
authors.initials: NR
authors.lastname: Choi
authors.affiliation: Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea.
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea; Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea.
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Jung
authors.affiliation: Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea.
authors.forename: Cheol Yi
authors.initials: CY
authors.lastname: Hong
authors.affiliation: Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea.
authors.forename: Manh-Cuong
authors.initials: MC
authors.lastname: Vo
authors.affiliation: Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea.
authors.forename: My-Dung
authors.initials: MD
authors.lastname: Hoang
authors.affiliation: Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea.
authors.forename: Hyeoung-Joon
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea; Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea. Electronic address: drjejung@chonnam.ac.kr.
authors.forename: Je-Jung
authors.initials: JJ
authors.lastname: Lee
mesh_terms: D051339:Actin Depolymerizing Factors / Q000378:metabolism*; D000251:Adenosine Triphosphatases; D020013:Calcium Signaling / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology; D053760:Interleukin-23 Subunit p19 / Q000378:metabolism; D009369:Neoplasms / Q000628:therapy; D011070:Poly I-C / Q000494:pharmacology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D051339:Actin Depolymerizing Factors; C508609:IL10 protein, human; C508585:IL1B protein, human; C508840:IL23A protein, human; D053583:Interleukin-1beta; D053760:Interleukin-23 Subunit p19; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma; D000251:Adenosine Triphosphatases; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506946:ATP2A2 protein, human; D011070:Poly I-C
keywords: SERCA2; chemotaxis; dendritic cell; migration