上原記念生命科学財団研究報告集, 34 (2020)ୖཎグᛕ⏕࿨⛉Ꮫ㈈ᅋ◊✲ሗ࿌㞟, 34㸦2020㸧

137. ࡀࢇච␿ᛂ⟅ࢆไᚚࡍࡿ DNA ಟ᚟ᛂ⟅ࡢゎ᫂బ⸨ ᾈኸ⩌㤿኱Ꮫ 㔜⢏Ꮚ⥺་Ꮫ◊✲ࢭࣥࢱ࣮ ་Ꮫ⏕≀Ꮫ㒊㛛Key words㸸⭘⒆ච␿㸪ᨺᑕ⥺἞⒪㸪㔜⢏Ꮚ⥺἞⒪㸪PD-L1㸪DNA ᦆയࢩࢢࢼࣝ⥴ ゝච␿ࢳ࢙ࢵࢡ࣏࢖ࣥࢺ㜼ᐖ๣࡛࠶ࡿᢠ PD-1㸭PD-L1 ᢠయࡣࠊ᪂ࡓ࡞ࡀࢇ἞⒪ࡢᰕ࡜ࡋ࡚኱ࡁ࡞ὀ┠ࢆ㞟ࡵ࡚࠸ࡿࠋ
ࡋ࠿ࡋᢠ PD-1㸭PD-L1 ᢠయ༢⊂࡛ࡣࠊ㧗࠸᭷ຠᛶࡀᚓࡽࢀࡿࡢࡣ୍㒊ࡢᝈ⪅࡟㝈ࡽࢀࡿࡇ࡜ࡶ᫂ࡽ࠿࡟࡞ࡗ࡚ࡁࡓࠋ
ࡑࡢࡓࡵࠊᨺᑕ⥺἞⒪ࡸ໬Ꮫ⒪ἲ࡜࠸ࡗࡓᚑ᮶ࡢࡀࢇ἞⒪࡜ࡢే⏝࡟ࡼࡿຠᯝࡢቑឤࡀᮇᚅࡉࢀࠊ⌧ᅾୡ⏺୰࡛ᩘከࡃࡢ⮫ᗋヨ㦂ࡀ㐍⾜୰࡛࠶ࡿࠋࡑࡢ⫼ᬒ࡜ࡋ࡚ࠊࡇࢀࡲ࡛࡟ࠊᨺᑕ⥺἞⒪ࡀᢠ⭘⒆ච␿ࢆάᛶ໬ࡍࡿࡇ࡜ࠊ⭘⒆⣽⬊ࡢ
PD-L1 Ⓨ⌧ࢆㄏᑟࡍࡿࡇ࡜ࠊࡉࡽ࡟⭘⒆⛣᳜࣐࢘ࢫ࡟࠾࠸࡚ᨺᑕ⥺἞⒪࡜ᢠ PD-1㸭PD-L1 ᢠయࡢే⏝ࡀࠊࡑࢀࡒࢀࡢ
༢⊂἞⒪࡜ẚ㍑ࡋ㧗࠸἞⒪ຠᯝࢆⓎ᥹ࡍࡿࡇ࡜࡞࡝ࡀ᫂ࡽ࠿࡟࡞ࡗ࡚࠸ࡿ㹙1㸪2㹛ࠋࡲࡓ」ᩘࡢ⮫ᗋヨ㦂࠿ࡽࠊ    
ᢠ PD-1㸭PD-L1 ᢠయࡣࠊPD-L1 Ⓨ⌧⋡ࡀ㧗࠸⭘⒆࡟ᑐࡋ࡚≉࡟᭷ຠ࡛࠶ࡿ࡜⪃࠼ࡽࢀ࡚࠸ࡿ㹙3㹛ࠋ௨ୖ࠿ࡽࠊ   ᢠ PD-1㸭PD-L1 ᢠయ࡜ᨺᑕ⥺἞⒪ࡢే⏝⒪ἲࢆ᭱㐺໬ࡍࡿୖ࡛ࠊᨺᑕ⥺἞⒪࡟ࡼࡿ PD-L1 Ⓨ⌧ไᚚᶵᵓࡢゎ᫂ࡣ 㔜せ࡞ㄢ㢟࡛࠶ࡿࠋከࡃࡢ๓⮫ᗋࣔࢹࣝࡢ◊✲࡟ࡼࡾࠊᨺᑕ⥺↷ᑕᚋ࡟ PD-1㸭PD-L1 ⤒㊰ࡀάᛶ໬ࡉࢀࡿࡇ࡜ࡣ᫂ࡽ࠿࡟࡞ࡾࡘࡘ࠶ࡿ୍᪉࡛ࠊࡑࡢศᏊᶵᵓࡢゎ᫂ࡣ୙༑ศ࡛࠶ࡗࡓࠋᡃࠎࡣࡇࢀࡲ࡛࡟ࠊᨺᑕ⥺㸦X ⥺㸧↷ᑕࢆཷࡅࡓࡀࢇ⣽⬊࡟࠾ࡅࡿ DNA஧ᮏ㙐ษ᩿㸦double-strand break㸸DSB㸧ᚋࡢ DNA ಟ᚟ࢩࢢࢼࣝᛂ⟅࡟╔┠ࡋࠊDNA ᦆയ౫Ꮡⓗ࡞ PD-L1 Ⓨ⌧ ไᚚ࣓࢝ࢽࢬ࣒ࢆሗ࿌ࡋࡓ㹙4㹛ࠋࡑࡇ࡛ᮏ◊✲࡛ࡣࠊ㏆ᖺࡢಖ㝤㐺⏝ࡢᣑ኱࡞࡝ࠊᚎࠎ࡟⮫ᗋ࡟࠾ࡅࡿ㔜せᛶࢆቑࡋ࡚࠸ࡿ㔜⢏Ꮚ⥺↷ᑕ࡟╔┠ࡋࠊ㔜⢏Ꮚ⥺↷ᑕᚋࡢ DNA ᦆയ࡟ㄏⓎࡉࢀࡿࡀࢇ⣽⬊⭷⾲㠃ୖࡢ PD-L1 Ⓨ⌧ㄪ⠇ᶵᵓࡢ ゎ᫂ࢆ┠ᣦࡋࡓࠋᮏ◊✲ࡢ㐩ᡂࡣࠊ㔜⢏Ꮚ⥺἞⒪ᚋࡢ⭘⒆࡟࠾࠸࡚ᢠ PD-1㸭PD-L1 ᢠయ἞⒪ࡀ࡝ࡢࡼ࠺࡟ຠᯝࢆ  Ⓨ᥹ࡍࡿ࠿ࢆ⌮ゎࡍࡿࡇ࡜࡟⧅ࡀࡾࠊࡦ࠸࡚ࡣ἞⒪๓ຠᯝண ࡢⓎᒎࡸ㔜⢏Ꮚ⥺἞⒪࡜ච␿ࢳ࢙ࢵࢡ࣏࢖ࣥࢺ㜼ᐖ๣ࡢే⏝࡜࠸࠺᪂ࡓ࡞ࡀࢇ἞⒪ᡓ␎ࡢᥦ᱌࡟ࡶ㈉⊩࡛ࡁࡿ࡜⪃࠼࡚࠸ࡿࠋ᪉ ἲ1㸬 㔜⢏Ꮚ⥺㸦Ⅳ⣲࢖࢜ࣥ⥺㸧↷ᑕ࡟ࡼࡿ PD-L1 Ⓨ⌧ไᚚᶵᵓࡢゎ᫂ࣄࢺ㦵⫗⭘⣽⬊ᰴ㸦U2OS㸧ࠊࣄࢺங⒴⣽⬊ᰴ㸦MCF-7㸧ࣄࢺ኱⭠⒴⣽⬊ᰴ㸦HCT116㸧ࢆ౑⏝ࡋࡓࠋⅣ⣲࢖࢜ࣥ⥺↷ᑕࡣࠊ⩌㤿኱Ꮫ㔜⢏Ꮚ⥺་Ꮫࢭࣥࢱ࣮࡟࡚ࠊ࢚ࢿࣝࢠ࣮290 MeV/n ࡢࣔࣀࣆ࣮ࢡ↷ᑕ㸦⥺࢚ࢿࣝࢠ࣮௜୚㸹LET ࢆࠊࡑࢀࡒࢀ 13ࠊ20ࠊ40ࠊ60 ࡟タᐃ㸧࡟࡚⾜ࡗࡓࠋᑐ↷⩌ࡢ X ⥺↷ᑕࡣ 100 kVpࠊ20 mA ࡟࡚⾜࠸ࠊ㖡ࡲࡓࡣ     ࢔࣑ࣝࢽ࣒࢘ࣇ࢕ࣝࢱ࣮ࢆ⏝࠸ࡓࠋ⥺㔞⋡ࡣ 0.5 Gy㸭ศ࡛࠶ࡗࡓࠋPD-L1 Ⓨ⌧࡟࠾ࡅࡿ DNA ᦆയࢩࢢࢼࣝࡢ㛵୚ࢆ᫂ࡽ࠿࡟ࡍࡿࡓࡵࠊATRࠊChk1 ࡟╔┠ࡋࠊATR 㜼ᐖ๣㸦VE821㸹Axon Medchem㸧ࠊChk1 㜼ᐖ๣㸦MK8776㸹AdooQ
Bioscience㸧ࢆࠊⅣ⣲࢖࢜ࣥ⥺࠾ࡼࡧ X ⥺↷ᑕࡢ 30 ศ๓࡟ᢞ୚ࡋࡓࠋPD-L1 Ⓨ⌧㔞ࡣ Western blotࠊFlow cytometryࠊࣜ࢔ࣝࢱ࢖࣒ PCR ࡟࡚ゎᯒࡋࡓࠋࡉࡽ࡟ࠊ㉸㧗ゎീᗘ㢧ᚤ㙾ࢆ⏝࠸࡚ࠊⅣ⣲࢖࢜ࣥ⥺↷ᑕᚋࡢ PD-L1 Ⓨ⌧ࡢ୕ḟඖⓗศᕸࢆゎᯒࡋࡓࠋ1ୖཎグᛕ⏕࿨⛉Ꮫ㈈ᅋ◊✲ሗ࿌㞟, 34㸦2020㸧㻌⤖ ᯝ1㸬Ⅳ⣲࢖࢜ࣥ⥺↷ᑕ࡟ࡼࡿ PD-L1 Ⓨ⌧ㄏᑟⅣ⣲࢖࢜ࣥ⥺↷ᑕ࡟ࡼࡾࠊ⣽⬊⭷⾲㠃ࣞ࣋ࣝࠊࢱࣥࣃࢡࣞ࣋ࣝࠊmRNA ࣞ࣋ࣝ඲࡚࡟࠾࠸࡚ PD-L1 Ⓨ⌧ࡀㄏᑟ  ࡉࢀࡓ㸦ᅗ 1㸧ࠋࡇࡢ PD-L1 Ⓨ⌧ㄏᑟࣞ࣋ࣝࡣࠊྠ⥺㔞ࡢ X ⥺࡜ẚ㍑ࡍࡿ࡜᭷ព࡟㧗࠿ࡗࡓࠋࡉࡽ࡟Ⅳ⣲࢖࢜ࣥ⥺     10 Gy ↷ᑕ࡟ࡼࡿ PD-L1 Ⓨ⌧ࣞ࣋ࣝࡣࠊLET ࡟౫Ꮡࡋ࡚ஹ㐍ࡋࡓࠋࡉࡽ࡟㉸㧗ゎീᗘ㢧ᚤ㙾࡟ࡼࡿ⣽⬊⭷⾲㠃ࡢ 
PD-L1 Ⓨ⌧ࡢ୕ḟඖⓗศᕸࡢゎᯒ࡛ࡣࠊPD-L1 ࢫ࣏ࢵࢺᩘࡣࠊX ⥺↷ᑕᚋ࡜ẚ㍑ࡋⅣ⣲࢖࢜ࣥ⥺↷ᑕᚋ࡛᭷ព࡟ୖ᪼
ࡋ࡚࠸ࡓ㸦ᅗ 2㸧ࠋ୍᪉࡛ࠊPD-L1 ࢫ࣏ࢵࢺࡢయ✚࡟ࡣࠊ୧⪅࡟࠾࠸࡚᭷ពᕪࢆㄆࡵ࡞࠿ࡗࡓࠋb)

45433221ۛ IR X 13 20 40 60

010 Gy C-ion(LET keV/m)ۛ IR 13

1.5

10 Gy C-ion(LET keV/m)

20 4060
PD-L1

1PARP-1

0.5Actin(loading)cleaved0ۛ IR X 20 60

10 Gy C-ion(LET keV/m)

2R012.5

ۛ

IRyG

10-…

6-I5c)U2OS

X…

MCF-7mRNA expression levels(relative to control)

MFI (x103)(PD-L1 - Isotype)

U2OSynioraXC- 60)
yG T
10 (LECa)ᅗ 1㸬Ⅳ⣲࢖࢜ࣥ⥺↷ᑕ࡟ࡼࡾ PD-L1 Ⓨ⌧ࡀㄏᑟࡉࢀࡿ
ࣄࢺ⭘⒆⣽⬊ᰴᑐࡍࡿⅣ⣲࢖࢜ࣥ⥺↷ᑕࡣࠊྠࡌ⥺㔞ࡢ X ⥺࡜ẚ㍑ࡋࠊࡼࡾ㧗ᗘ࡟ PD-L1 Ⓨ⌧ࢆㄏᑟࡋࡓࠋ࠸ࡎࢀࡢゎᯒࡶࠊⅣ⣲࢖࢜ࣥ⥺↷ᑕ࠿ࡽ 48 ᫬㛫ᚋ࡟⾜࡞ࡗࡓࠋa㸧Flow cytometry ࡢ⤖ᯝࠋb㸧ࣜ࢔ࣝࢱ࢖࣒ PCR ࡢ⤖ᯝࠋc㸧Western blot ࡢ⤖ᯝࠋ⤫ィ᳨ᐃࡣࠊGraphpad Prism 7.0 ࡟ࡼࡾ t-test ࢆ⏝࠸࡚⾜ࡗࡓ㸦*P 㸺0.05ࠊ**P㸺0.01ࠊ    ࠋMFI㸸median fluorescence intensity㸦MFI㸸PD-L1 – isotype㸧
ࠋ***P㸺0.001㸧

N.T
NT5 m5 m5 mc)

0.06

Volume of PD-L1 spot
(μm3)

15

Number of PD-L1 spot(x1000)b)

10 Gy
Gy C-ionC
10(LET60)

10 G
Gy X-rayX1050

P = 0.31
P = 0.71

0.04

0.02

y
Xra

-IR-IRXray(L C-ioET n60)0(L C-ioET n60)a)

ᅗ 2㸬ᨺᑕ⥺↷ᑕ࡟ࡼࡾㄏᑟࡉࢀࡿ PD-L1 ࡢ✵㛫ⓗศᕸa㸧㉸㧗ゎീᗘ㢧ᚤ㙾࡛᧜ᙳࡋࡓ௦⾲ⓗ⏬ീࠋb㸧Ⅳ⣲࢖࢜ࣥ⥺↷ᑕᚋࡣࠊX ⥺↷ᑕᚋࡼࡾࡶ᭷ព࡟ PD-L1 ࢫ࣏ࢵࢺᩘࡀ㧗࠿ࡗࡓࠋc㸧PD-L1 ࢫ࣏ࢵࢺ࠶ࡓࡾࡢయ✚ࡣࠊⅣ⣲࢖࢜ࣥ⥺↷ᑕ࡛ࡶ X ⥺↷ᑕ࡛ࡶ᭷ពᕪࡀ࡞࠿ࡗࡓࠋ⤫ィ᳨ᐃࡣࠊGraphpad Prism 7.0 ࡟ࡼࡾ t-test ࢆ⏝࠸࡚⾜ࡗࡓ㸦*P㸺0.05ࠊ**P㸺0.01ࠊ***P㸺0.001㸧
ࠋ2ୖཎグᛕ⏕࿨⛉Ꮫ㈈ᅋ◊✲ሗ࿌㞟, 34㸦2020㸧
㻌2㸬DNA ᦆയࢩࢢࢼࣝ࡟ࡼࡿࠊⅣ⣲࢖࢜ࣥ⥺↷ᑕᚋࡢ PD-L1 Ⓨ⌧ไᚚඛ⾜◊✲࡟࡚ X ⥺↷ᑕᚋࡢ PD-L1 Ⓨ⌧ㄏᑟ࡬ࡢ㛵୚ࡀ᫂ࡽ࠿࡟࡞ࡗ࡚࠸ࡓࠊDNA ᦆയࢩࢢࢼࣝ࡟╔┠ࡋࡓࠋ  Ⅳ⣲࢖࢜ࣥ⥺࠾ࡼࡧ X ⥺↷ᑕᚋࡢ Chk1 ࣜࣥ㓟໬ࣞ࣋ࣝࢆẚ㍑ࡋࡓ࡜ࡇࢁࠊⅣ⣲࢖࢜ࣥ⥺↷ᑕᚋࡢ᪉ࡀࡼࡾ㧗ᗘ࡟ ࣜࣥ㓟໬ࢆㄆࡵࡓࠋࡉࡽ࡟ࠊChk1 㜼ᐖ๣ࢆຍ࠼ࡿࡇ࡜࡛ࠊⅣ⣲࢖࢜ࣥ⥺↷ᑕᚋࡢ PD-L1 Ⓨ⌧ㄏᑟࡣ᭷ព࡟ᢚไ   ࡉࢀࡓ㸦ᅗ 3㸧
ࠋChk1 ࡢୖὶ࡟࠶ࡓࡿ ATR 㜼ᐖ๣ࢆຍ࠼࡚ࡶࠊྠᵝ࡟Ⅳ⣲࢖࢜ࣥ⥺↷ᑕᚋࡢ PD-L1 Ⓨ⌧ㄏᑟࡣ   ᢚไࡉࢀࡓࠋ
ࡉࡽ࡟ࠊDNA ᦆയࢩࢢࢼࣝࡢୗὶࡢ PD-L1 Ⓨ⌧ไᚚᶵᵓ࡜ࡋ࡚ࠊᚑ᮶ PD-L1 Ⓨ⌧ㄏᑟ⤒㊰࡜ࡋ࡚▱ࡽࢀ࡚࠸ࡿࠊ
STAT-IRF1 ⤒㊰ࡢ㛵୚ࡶゎᯒࡋࡓࠋࡑࡢ⤖ᯝࠊⅣ⣲࢖࢜ࣥ⥺↷ᑕᚋ࡟ࡣ STAT1/3 ࡢࣜࣥ㓟໬ஹ㐍ࠊ࠾ࡼࡧ IRF1 Ⓨ⌧ࡢஹ㐍ࢆㄆࡵࡓ㸦ᅗ 4㸧ࠋ

C-ion(LET 60)
2 5 10X-ray2

ۛ IR510b)

DMSO

–Gy

Chk1i+ –10 Gy C-ion+ (LET 60)

pChk1

PD-L1

Chk1

PARP-1cleavedActin(loading)

Actin(loading)

4c)
MFI (x103)(PD-L1 - Isotype)

a)

3
2
1

0
10 Gy C-ion(LET 60)–++Chk1i

ᅗ 3㸬Ⅳ⣲࢖࢜ࣥ⥺↷ᑕᚋࡢ PD-L1 Ⓨ⌧ㄏᑟࡣ DNA ᦆയࢩࢢࢼࣝ࡟ࡼࡾไᚚࡉࢀࡿa㸧ྠࡌ⥺㔞࡛ࡢẚ㍑࡛ࡣࠊⅣ⣲࢖࢜ࣥ⥺↷ᑕᚋࡢ᪉ࡀ᭷ព࡟ Chk1 ࣜࣥ㓟໬ࡢㄏᑟࢆㄆࡵࡓࠋb, c㸧Chk1 㜼ᐖ๣࡟ࡼࡾⅣ⣲࢖࢜ࣥ⥺↷ᑕᚋࡢ PD-L1 Ⓨ⌧ㄏᑟࡀᢚไࡉࢀࡓࠋ
ࠋ⤫ィ᳨ᐃࡣࠊGraphpad Prism 7.0 ࡟ࡼࡾ t-test ࢆ⏝࠸࡚⾜ࡗࡓ㸦*P㸺0.05ࠊ**P㸺0.01ࠊ***P㸺0.001㸧

a)ۛ IR25b)

C-ion(LET 60)

X-ray102510Gy
IRF1c)DMSO– +ATRi–+STAT1 pY701
STAT110 Gy C-ion(LET 60)

DMSO– +Chk1i–+10 Gy C-ion(LET 60)
IRF1

IRF1

STAT1 pY701

Actin(loading)

STAT1Actin(loading)

H3K9me3(loading)ᅗ 4㸬Ⅳ⣲࢖࢜ࣥ⥺↷ᑕᚋࡢ PD-L1 Ⓨ⌧ㄏᑟࡣ STAT-IRF1 ⤒㊰ࢆ௓ࡍࡿa㸧 ྠࡌ⥺㔞࡛ࡢẚ㍑࡛ࡣࠊⅣ⣲࢖࢜ࣥ⥺↷ᑕᚋࡢ᪉ࡀ᭷ព࡟ IRF1 Ⓨ⌧࠾ࡼࡧ STAT1 ࣜࣥ㓟໬ࡢㄏᑟࢆㄆࡵࡓࠋ
b, c㸧 ATRࠊChk1 㜼ᐖ๣࡟ࡼࡾⅣ⣲࢖࢜ࣥ⥺↷ᑕᚋࡢ IRF1 Ⓨ⌧ࡀᢚไࡉࢀࡓࠋ⪃ ᐹᮏ◊✲ࡢ⤖ᯝ࠿ࡽࠊⅣ⣲࢖࢜ࣥ⥺↷ᑕ࡟ࡼࡿ PD-L1 Ⓨ⌧ㄏᑟࡣࠊX ⥺࡜ྠᵝࠊATR㸭Chk1 ࡜࠸ࡗࡓ DNA ᦆയ  ࢩࢢࢼࣝ࡜ࠊࡑࡢୗὶ࡛ࡢ STAT㸫IRF1 ⤒㊰ࢆ௓ࡋ࡚ไᚚࡉࢀࡿࡇ࡜ࡀ᫂ࡽ࠿࡟࡞ࡗࡓࠋࡋ࠿ࡋⅣ⣲࢖࢜ࣥ⥺↷ᑕᚋࡢ᪉ࡀ PD-L1 Ⓨ⌧ࣞ࣋ࣝࡣ᭷ព࡟㧗࠿ࡗࡓࠋࡑࡢ⌮⏤࡜ࡋ࡚ࡣࠊྠࡌ⤒㊰࡛ࡣ࠶ࡿࡀࠊⅣ⣲࢖࢜ࣥ⥺↷ᑕ࡛ࡣ X ⥺ ࡼࡾࡶ」㞧࡞ DNA ᦆയࡀㄏᑟࡉࢀࡿࡓࡵࠊࡇࡢ⤒㊰ࡢάᛶ໬ࡀᙉࡃࠊࡑࢀ࡟ࡼࡗ࡚ࠊࡼࡾ㧗ᗘ࡟ PD-L1 Ⓨ⌧ࡀㄏᑟࡉࢀࡿ࡜⪃࠼ࡽࢀࡓࠋDNA ᦆയࢩࢢࢼࣝࡣⅣ⣲࢖࢜ࣥ⥺἞⒪࡜ᢠ PD-1㸭PD-L1 ᢠయ἞⒪ే⏝᫬ࡢ἞⒪ຠᯝቑឤࡢ
ࡓࡵࡢᶆⓗࡢ୍ࡘ࡜ࡋ࡚ᮇᚅ࡛ࡁࠊࡉࡽ࡟ࡇࢀࡽࡢ PD-L1 Ⓨ⌧ไᚚ⣔࡟ኚ␗ࢆᣢࡘࡀࢇᝈ⪅࡛ࡣࠊ㔜⢏Ꮚ⥺἞⒪࡜    
ᢠ PD-1㸭PD-L1 ᢠయࡢే⏝἞⒪ࡀࡼࡾ᭷ຠ࡛࠶ࡿྍ⬟ᛶࡀ♧၀ࡉࢀࡓࠋᮏ◊✲⤖ᯝࡣࠊⅣ⣲࢖࢜ࣥ⥺἞⒪࡜    ච␿ࢳ࢙ࢵࢡ࣏࢖ࣥࢺ㜼ᐖ๣ࡢే⏝࡜࠸࠺ࠊ᪂ࡓ࡞ࡀࢇ἞⒪ᡓ␎ࡢጇᙜᛶࢆᨭᣢࡍࡿࡶࡢ࡛࠶ࡿࠋ
3ୖཎグᛕ⏕࿨⛉Ꮫ㈈ᅋ◊✲ሗ࿌㞟, 34㸦2020㸧㻌ඹྠ◊✲⪅࣭ㅰ㎡ᮏ◊✲ࡣࠊ⩌㤿኱Ꮫᮍ᮶ඛ➃◊✲ᶵᵓࡢᰘ⏣῟ྐㅮᖌ࡜ࡢඹྠ◊✲࡟ࡼࡗ࡚⾜ࢃࢀࡓࠋᩥ ⊩
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4㸧 Hiro Sato, Atsuko Niimi, Takaaki Yasuhara, Tiara Bunga Mayang Permata, Yoshihiko Hagiwara, Mayu Isono ,Endang Nuryadi, Ryota Sekine, Takahiro Oike, Sangeeta Kakoti, Yuya Yoshimoto, Kathryn D Held, Yoshiyuki
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