PMID- 23600320
OWN - NLM
STAT- MEDLINE
DCOM- 20130718
LR  - 20130422
IS  - 0016-254X (Print)
IS  - 0016-254X (Linking)
VI  - 104
IP  - 1
DP  - 2013 Jan
TI  - CD4 T cell-mediated masking effects of the immunogenicity of tumor-associated 
      antigens are qualitatively and quantitatively different depending on the 
      individual antigens.
PG  - 1-14
AB  - The use of cancer immunotherapy as part of multidisciplinary therapies for cancer 
      is a promising strategy for the cure of advanced cancer patients. In cancer 
      immunotherapy, the effective priming of tumor-associated antigen (TAA)-specific 
      CD8+ T cells is essential, and therefore, the appropriate selection of the best 
      peptide for targeting the cancer is a most important concern. One criticism in 
      the selection of a TAA is the immunogenicity of the TAA, the vaccination of which 
      effectively elicits clinical responses. However, the critical basic immunological 
      factors that affect the differences in the immunogenicity of TAAs remain to be 
      elucidated. Here we found that CD4 T-cell responses suppressed the immunogenicity 
      of the concomitant TAA in a murine melanoma model in which intratumoral activated 
      dendritic therapy (ITADT) was used for treatment of the established cancer, and 
      we observed that the antitumor effects were largely dependent on the CD8 T-cell 
      response. CD4 T-cell depletion simply enhanced the tyrosinase-related protein 
      (TRP)-2(180-188) peptide-specific cytotoxic T-cell (CTL) responses, and CD4 
      T-cell depletion provided immunogenicity for mgp100(25-33) peptide, to which a 
      CTL response could not be detected at all in CD4 T-cell-intact mice in the early 
      therapeutic phase. Further, the mgp100(25-33) peptide-specific CTL response again 
      became undetectable after the recovery of CD4 T cells in previously CD4-depleted, 
      tumor-eradicated mice, whereas the TRP-2(180-188) peptide-specific CTL response 
      was still much stronger in CD4-depleted mice than in CD4-intact mice. These 
      findings suggest that the CD4 T cell-mediated masking effects of the 
      immunogenicity of tumor-associated antigens are qualitatively and quantitatively 
      different depending on the individual antigens.
FAU - Okano, Shinji
AU  - Okano S
AD  - Division of Pathophysiological and Experimental Pathology, Department of 
      Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 
      812-8582, Japan. okap@surg2.med.kyushu-u.ac.jp
FAU - Matsumoto, Yoshihiro
AU  - Matsumoto Y
FAU - Yoshiya, Shohei
AU  - Yoshiya S
FAU - Yamashita, Yo-ichi
AU  - Yamashita Y
FAU - Harimoto, Norifumi
AU  - Harimoto N
FAU - Ikegami, Toru
AU  - Ikegami T
FAU - Shirabe, Ken
AU  - Shirabe K
FAU - Harada, Mamoru
AU  - Harada M
FAU - Yoshikai, Yasunobu
AU  - Yoshikai Y
FAU - Maehara, Yoshihiko
AU  - Maehara Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Japan
TA  - Fukuoka Igaku Zasshi
JT  - Fukuoka igaku zasshi = Hukuoka acta medica
JID - 9423321
RN  - 0 (Antigens, Neoplasm)
SB  - IM
MH  - Animals
MH  - Antigens, Neoplasm/*immunology
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Cell Line, Tumor
MH  - Dendritic Cells/immunology
MH  - Female
MH  - Flow Cytometry
MH  - Immunotherapy/methods
MH  - Melanoma, Experimental/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
EDAT- 2013/04/23 06:00
MHDA- 2013/07/19 06:00
CRDT- 2013/04/23 06:00
PHST- 2013/04/23 06:00 [entrez]
PHST- 2013/04/23 06:00 [pubmed]
PHST- 2013/07/19 06:00 [medline]
PST - ppublish
SO  - Fukuoka Igaku Zasshi. 2013 Jan;104(1):1-14.