PMID- 27619885
OWN - NLM
STAT- MEDLINE
DCOM- 20171211
LR  - 20190112
IS  - 1756-9966 (Electronic)
IS  - 0392-9078 (Print)
IS  - 0392-9078 (Linking)
VI  - 35
IP  - 1
DP  - 2016 Sep 13
TI  - Tumoricidal efficacy coincides with CD11c up-regulation in antigen-specific 
      CD8(+) T cells during vaccine immunotherapy.
PG  - 143
LID - 10.1186/s13046-016-0416-x [doi]
LID - 143
AB  - BACKGROUND: Dendritic cells (DCs) mount tumor-associated antigens (TAAs), and the 
      double-stranded RNA adjuvant Poly(I:C) stimulates Toll-like receptor 3 (TLR3) 
      signal in DC, which in turn induces type I interferon (IFN) and interleukin-12 
      (IL-12), then cross-primes cytotoxic T lymphocytes (CTLs). Proliferation of CTLs 
      correlates with tumor regression. How these potent cells expand with high quality 
      is crucial to the outcome of CTL therapy. However, good markers reflecting the 
      efficacy of DC-target immunotherapy have not been addressed. METHODS: Using an 
      EG7 (ovalbumin, OVA-positive) tumor-implant mouse model, we examined what is a 
      good marker for active CTL induction in treatment with Poly(I:C)/OVA. RESULTS: 
      Simultaneous administration of Poly(I:C) and antigen (Ag) OVA significantly 
      increased a minor population of CD8(+) T cells, that express CD11c in lymphoid 
      and tumor sites. The numbers of the CD11c(+) CD8(+) T cells correlated with those 
      of induced Ag-specific CD8(+) T cells and tumor regression. The CD11c(+) CD8(+) T 
      cell moiety was characterized by its high killing activity and IFN-gamma-producing 
      ability, which represent an active phenotype of the effector CTLs. Not only a 
      TLR3-specific (TICAM-1-dependent) signal but also TLR2 (MyD88) signal in DC 
      triggered the expansion of CD11c(+) CD8(+) T cells in tumor-bearing mice. 
      Notably, human CD11c(+) CD8(+) T cells also proliferated in peripheral blood 
      mononuclear cells (PBMC) stimulated with cytomegalovirus (CMV) Ag. CONCLUSIONS: 
      CD11c expression in CD8(+) T cells reflects anti-tumor CTL activity and would be 
      a marker for immunotherapeutic efficacy in mouse models and probably cancer 
      patients as well.
FAU - Takeda, Yohei
AU  - Takeda Y
AD  - Department of Microbiology and Immunology, Hokkaido University Graduate School of 
      Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo, 060-8638, Japan.
FAU - Azuma, Masahiro
AU  - Azuma M
AD  - Department of Microbiology and Immunology, Hokkaido University Graduate School of 
      Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo, 060-8638, Japan.
FAU - Matsumoto, Misako
AU  - Matsumoto M
AD  - Department of Microbiology and Immunology, Hokkaido University Graduate School of 
      Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo, 060-8638, Japan.
FAU - Seya, Tsukasa
AU  - Seya T
AD  - Department of Microbiology and Immunology, Hokkaido University Graduate School of 
      Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo, 060-8638, Japan. 
      seya-tu@pop.med.hokudai.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160913
PL  - England
TA  - J Exp Clin Cancer Res
JT  - Journal of experimental & clinical cancer research : CR
JID - 8308647
RN  - 0 (CD11c Antigen)
RN  - 0 (Cancer Vaccines)
RN  - 9006-59-1 (Ovalbumin)
RN  - O84C90HH2L (Poly I-C)
SB  - IM
MH  - Animals
MH  - CD11c Antigen/*metabolism
MH  - CD8-Positive T-Lymphocytes/immunology/*transplantation
MH  - Cancer Vaccines/immunology/therapeutic use
MH  - Dendritic Cells/immunology
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Immunotherapy
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neoplasms, Experimental/immunology/*therapy
MH  - Ovalbumin/*administration & dosage
MH  - Poly I-C/*administration & dosage
MH  - Up-Regulation
MH  - Xenograft Model Antitumor Assays
PMC - PMC5020536
OTO - NOTNLM
OT  - Adjuvant
OT  - Antitumor immunotherapy
OT  - CD11c+ CD8+ T cell
OT  - CTL
OT  - Poly(I:C)
OT  - TLR3
OT  - Therapeutic marker
EDAT- 2016/09/14 06:00
MHDA- 2017/12/12 06:00
PMCR- 2016/09/13
CRDT- 2016/09/14 06:00
PHST- 2016/06/14 00:00 [received]
PHST- 2016/09/01 00:00 [accepted]
PHST- 2016/09/14 06:00 [entrez]
PHST- 2016/09/14 06:00 [pubmed]
PHST- 2017/12/12 06:00 [medline]
PHST- 2016/09/13 00:00 [pmc-release]
AID - 10.1186/s13046-016-0416-x [pii]
AID - 416 [pii]
AID - 10.1186/s13046-016-0416-x [doi]
PST - epublish
SO  - J Exp Clin Cancer Res. 2016 Sep 13;35(1):143. doi: 10.1186/s13046-016-0416-x.