PMID- 29696308
OWN - NLM
STAT- MEDLINE
DCOM- 20181120
LR  - 20201221
IS  - 1432-0851 (Electronic)
IS  - 0340-7004 (Print)
IS  - 0340-7004 (Linking)
VI  - 67
IP  - 7
DP  - 2018 Jul
TI  - Role of MDA5 and interferon-I in dendritic cells for T cell expansion by 
      anti-tumor peptide vaccines in mice.
PG  - 1091-1103
LID - 10.1007/s00262-018-2164-6 [doi]
AB  - Cytotoxic T lymphocytes (CTLs) are effective components of the immune system 
      capable of destroying tumor cells. Generation of CTLs using peptide vaccines is a 
      practical approach to treat cancer. We have previously described a peptide 
      vaccination strategy that generates vast numbers of endogenous tumor-reactive 
      CTLs after two sequential immunizations (prime-boost) using poly-ICLC adjuvant, 
      which stimulates endosomal toll-like receptor 3 (TLR3) and cytoplasmic melanoma 
      differentiation antigen 5 (MDA5). Dendritic cells (DCs) play an important role 
      not only in antigen presentation but are critical in generating costimulatory 
      cytokines that promote CTL expansion. Poly-ICLC was shown to be more effective 
      than poly-IC in generating type-I interferon (IFN-I) in various DC subsets, 
      through its enhanced ability to escape the endosomal compartment and stimulate 
      MDA5. In our system, IFN-I did not directly function as a T cell costimulatory 
      cytokine, but enhanced CTL expansion through the induction of IL15. With 
      palmitoylated peptide vaccines, CD8alpha+ DCs were essential for peptide 
      crosspresentation. For vaccine boosts, non-professional antigen-presenting cells 
      were able to present minimal epitope peptides, but DCs were still required for 
      CTL expansions through the production of IFN-I mediated by poly-ICLC. Overall, 
      these results clarify the roles of DCs, TLR3, MDA5, IFN-I and IL15 in the 
      generation of vast and effective antitumor CTL responses using peptide and 
      poly-IC vaccines.
FAU - Sultan, Hussein
AU  - Sultan H
AD  - Cancer Immunology, Immunotherapy and Tolerance Program, Georgia Cancer Center, 
      Augusta University, 1410 Laney Walker Blvd., CN-4121, Augusta, GA, 30912, USA.
FAU - Wu, Juan
AU  - Wu J
AD  - Cancer Immunology, Immunotherapy and Tolerance Program, Georgia Cancer Center, 
      Augusta University, 1410 Laney Walker Blvd., CN-4121, Augusta, GA, 30912, USA.
FAU - Kumai, Takumi
AU  - Kumai T
AD  - Department of Otolaryngology, Head and Neck Surgery, Asahikawa Medical 
      University, Asahikawa, Japan.
FAU - Salazar, Andres M
AU  - Salazar AM
AD  - Oncovir, Inc., Washington, DC, USA.
FAU - Celis, Esteban
AU  - Celis E
AUID- ORCID: 0000-0001-8299-4480
AD  - Cancer Immunology, Immunotherapy and Tolerance Program, Georgia Cancer Center, 
      Augusta University, 1410 Laney Walker Blvd., CN-4121, Augusta, GA, 30912, USA. 
      ecelis@augusta.edu.
LA  - eng
GR  - R01 CA157303/CA/NCI NIH HHS/United States
GR  - R01CA157303/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180425
PL  - Germany
TA  - Cancer Immunol Immunother
JT  - Cancer immunology, immunotherapy : CII
JID - 8605732
RN  - 0 (Cancer Vaccines)
RN  - 0 (Interferon Inducers)
RN  - 0 (Interferon Type I)
RN  - 0 (TLR3 protein, mouse)
RN  - 0 (Toll-Like Receptor 3)
RN  - 0 (Vaccines, Subunit)
RN  - 25104-18-1 (Polylysine)
RN  - 7KYP9TKT70 (poly ICLC)
RN  - EC 3.6.1.- (Ifih1 protein, mouse)
RN  - EC 3.6.4.13 (Interferon-Induced Helicase, IFIH1)
RN  - K679OBS311 (Carboxymethylcellulose Sodium)
RN  - O84C90HH2L (Poly I-C)
SB  - IM
MH  - Animals
MH  - Cancer Vaccines/*administration & dosage
MH  - Carboxymethylcellulose Sodium/administration & dosage/analogs & derivatives
MH  - Dendritic Cells/drug effects/*immunology
MH  - Interferon Inducers/administration & dosage
MH  - Interferon Type I/*metabolism
MH  - Interferon-Induced Helicase, IFIH1/*physiology
MH  - Melanoma, Experimental/immunology/metabolism/pathology/*therapy
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Poly I-C/administration & dosage
MH  - Polylysine/administration & dosage/analogs & derivatives
MH  - T-Lymphocytes, Cytotoxic/drug effects/*immunology
MH  - Toll-Like Receptor 3/physiology
MH  - Tumor Cells, Cultured
MH  - Vaccination
MH  - Vaccines, Subunit/*administration & dosage
PMC - PMC6585404
MID - NIHMS1026500
OTO - NOTNLM
OT  - Dendritic cells
OT  - Interleukin-15
OT  - MDA5
OT  - Peptide vaccines
OT  - Poly-IC
OT  - Type-I interferon
COIS- A. Salazar is President and CEO of Oncovir, Inc. and is developing poly-ICLC 
      (Hiltonol ) for the clinic. Esteban Celis has filed patent applications based on 
      the use of synthetic peptides and poly-IC combinatorial vaccines. The rights of 
      the patent applications have been transferred to the Moffitt Cancer Center 
      (Tampa, FL). Other authors declare no conflict of interest.
EDAT- 2018/04/27 06:00
MHDA- 2018/11/21 06:00
PMCR- 2018/04/25
CRDT- 2018/04/27 06:00
PHST- 2017/12/18 00:00 [received]
PHST- 2018/04/20 00:00 [accepted]
PHST- 2018/04/27 06:00 [pubmed]
PHST- 2018/11/21 06:00 [medline]
PHST- 2018/04/27 06:00 [entrez]
PHST- 2018/04/25 00:00 [pmc-release]
AID - 10.1007/s00262-018-2164-6 [pii]
AID - 2164 [pii]
AID - 10.1007/s00262-018-2164-6 [doi]
PST - ppublish
SO  - Cancer Immunol Immunother. 2018 Jul;67(7):1091-1103. doi: 
      10.1007/s00262-018-2164-6. Epub 2018 Apr 25.