ƉuÖ@ɂlϐ

<strong>R </strong>
iww@wn ċzEƉuȊwj
emailF<a href="mailto:koyama@imed3.med.osaka-u.ac.jp">R</a>
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̈Zr[, <strong>7</strong>, e004 (2018)@<a href="http://dx.doi.org/10.7875/leading.author.7.e004">DOI: 10.7875/leading.author.7.e004</a>
Shohei Koyama: <strong>Adaptive and acquired resistance to cancer immunotherapies.</strong>

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<h2>v </h2>
@2012NɊěŌ`ɑ΂RPD-1R̂эRPD-L1R̗̂L񍐂ĈȗC킪ɂĂCFx͂߂Ƃ܂܂Ȃɑ΂Ɖu`FbN|CgjQɂ邪ƉuÖ@WIȎÖ@̂ЂƂƂėp悤ɂȂDۂɖƉu`FbN|CgjQɂ莡Â銳҂̑ɂƂȂĈƉuÖ@ɑ΂ƂƑt̓ȂǗႾłȂC͑tĂɂ炸ᇂđ傷Ǘ݂̑炩ɂꂽDȂC炪ƉuÖ@ɑ΂ϐǂ̂悤ȋ@ɂ萶̂ɂĂ͂܂sȓ_DM҂́C񏬍זExɑ΂RPD-1R̂ɂ邪ƉuÖ@ɂĒ̎Â̂̂ϐǗ̉͂CTזEɂPD-1ȊO̖Ɖu`FbN|Cg^pN̔̏㏸ɂƂȂTזE}㏞Iȋ@ɂĖ炩ɂD̃r[ɂẮCɍRPD-1R̂ɂ邪ƉuÖ@ɂĐϐCƂɊlϐɏœ_āČƂȂᇍזËqяh̖ƉuזËq̗̑ʂC̋@ɂĉD

<h2>͂߂</h2>
@2000N㏉̃qgɂ邪̃Qm͂̐iɂC̈`qɐψقɂVOïُȊٓIɗ}悤ȎÖ̊Ji݁CLi[[jQƂĊëᇂɑ΂LƂ炩ɂCQmÂɂŏ̃uCNX[ƂȂDx͑gDwIɐ_oזEɗR鏬זEƂȊO̔񏬍זExƂɕނ邪C񏬍זExCȂłCƂpx̍Bɂ<em>EGFR</em>`qC<em>ALK</em>`qC<em>ROS1</em>`qƂ`qɂē̕ʂ̕ψق`qǂ̗ZȂǂVOïُȊ邱Ƃ炩ɂꂽD̈`qψق͔x̑BɂL[v[[Ƃċ@\邱ƂhCo[ψقƂ΂邪Cꂼ̈`qψقɂVOïُȊٓIɑjQLi[[jQ򂪊JꂽD̓IȈ`qψق҂ɂẮC܂łƂÂ̌ʂƂĂRܕpÖ@ƔrāC̃Li[[jQ򂪔ɍt炷ƂChCo[ψقx̊҂̗\IɉP邱Ƃɐ<a href="#R1"><sup>1)</sup></a>D
@̈CVȉۑƂāCaR̒ɂ킽gpɂϐl̂Ɠ悤ɁCxזEhCo[ψقWIƂLi[[jQɑ΂͔N1Nőϐl邱Ƃ炩ɂꂽDɃQm͂ɂƂÂɂCϐ̋@̈ꕔ2IȈ`qψق̊lƂ̃p^[Ƃ킩<a href="#R2"><sup>2)</sup></a>Dϐ̊lƂۑ͂̂́CLi[[jQ̓hCo[ψق҂ɑ΂ɍLƂC݂ł́Cx̎ÂɂĔɑ傫ȖSĂDC̃hCo[ψقȂ҂ɑ΂L͖RĈ悤Ȋ҂ɑ΂ĂC܂ł̕WIȍR܂ɂ鎡Â𗽉킷悤ȐVȎÖ@̊J]܂ĂDɓoꂵ̂CƉu`FbN|CgjQɑ\邪ƉuÖ@ł<a href="#R3"><sup>3,4)</sup></a>D
@킪ɂāC񏬍זExɑ΂ŏɎgp\ɂȂƉu`FbN|CgjQ򂪍RPD-1R̂łD̎Â̌ʂ́ChCo[ψق҂ނȂ҂ɂčĈ̌ɂC̗R͎ᇂɂ`qψق̗ʁitumor mutation burdenFTMBjɂ邱Ƃ炩ɂChCo[ψق҂ɔׁChCo[ψقȂ҂ɂĂ͈`qψق̗ʂ葽ƂɊ֗^<a href="#R5"><sup>5,6)</sup></a>D`qψق̗ʂɂ͋i傫^ĂCi̍̂܂܈`qψق̗ʂэRPD-1R̂ɂt̍ɉe\<a href="#R5"><sup>5)</sup></a>Ci҂Ɍ₷Âł邱ƂꂽD̂̂Ci`qψق̗ʂ̂قɂCRPD-1R̂ɑ΂銴󐫂邢͔񊴎󐫂ɂ邳܂܂Ȉq񍐂ꂽD
@Ɖu`FbN|CgjQɊւЂƂ̓ƂāCÂtꍇC̎Â̌ʂR܂Li[[jQɂ킽莝邱Ƃ<a href="#R7"><sup>7)</sup></a>DCƉuÖ@ɂ蒷ɂ킽莡ÂꂽǗ̒~ςɂƂȂCM҂܂ޕ̌O[vɂCrIɂ킽tĂɂ炸CLi[[jQɂĔF߂悤ȑϐ̊lƉu`FbN|CgjQɂĂȂ炸邱Ƃ炩ɂꂽD܂ł̃Qm̐iɂƂÂLi[[jQ̊Jт̑ϐ̊l̋@̉𖾂ƂwiCƉuÖ@ɂϐ̊l̋@ɂĂᇍזẼQm͂̃Av[`i߂ꂽC܂ł̎Ö@Ƃ͈قȂCƉuÖ@̕WI͏h̖ƉuזEł邽߁CƉuזȄԂԂ̌o߂ŒǐՂ邱Ƃϐ̊l̋@̉𖾂ɂ͏dvł邱ƂꂽD
@ȏ̂悤ȔwiC̃r[ɂẮCɔ񏬍זExɑ΂RPD-1R̂ɂ邪ƉuÖ@ɂϐ̊l̋@ɏœ_āCŋ߁C炩ɂꂽmɂĉD
@ȂCƉuÖ@ɂẮC<a href="http://leading.lifesciencedb.jp/4-e005/" target="_blank">RE씎, ̈Zr[, <strong>4</strong>, e005 (2015)</a> QƂꂽD

<h2>1DƉu`FbN|Cg^pNт̑jQ</h2>
@ᇍזE̔jɋ@\C܂CƉu`FbN|CgjQ̕WIɂȂL[v[[TזEłDTזÉC{͐̂ɂ݂͑ᇍזÊ݂ɏoُȔ񎩌ȃ^pNٓIɔFCĕWIƂȂᇍזEj󂷂D̉ߒōŏɕKvƂȂ̂Cُȃ^pN̏`B鑤̍זEɂvgDK`q́imajor histocompatibility complexFMHCjƁCTזEɂêƂ̑ݍpłDۂɁĈ̂זEMHC𔭌邱Ƃɂُȃ^pN̏`B\͂C̓`B̃GLXp[głזEזE}Nt@[WȂǂ̍R񎦍זEłDR񎦍זEُ͈ȃ^pN̏𕪉yv`h̒fЂƂTזEɓ`BƓɁCTזEɂCD28hCD80CD86Ƃ^pN𔭌C`BTזED͋h^pNƂ΂CTזEɊɃANZpDCTזEɂ͊傤ǂ悭~悤u[Lp^pNɔDTזE͗}^pN𑍏̂ĖƉu`FbN|Cg^pNƂԁi<a href="#F1">}1</a>jD

<a name="F1"></a><div id="fig1-caption-text" style="display: none;"><strong>}1@TזE̔Ɖu`FbN|Cg^pNэRPD-1R̂̍p_</strong>
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2018/05/Koyama-7.e004-Fig.1.jpg" target="_blank">[Download]</a></div>[hs_figure id=1&amp;image=/wordpress/wp-content/uploads/2018/05/Koyama-7.e004-Fig.1.png&amp;caption=fig1-caption-text]

@ᇂɂĖɂȂ̂CR񎦍זEᇍזETזE̊}Ɖu`FbN|Cg^pNɕKvȏɍp邱ƂɂCTזEɂᇍזE̔j󂪏\ɂłȂƂłD̉ߏȃu[LՒf̂Ɖu`FbN|CgjQŁCƂɁCRPD-1R͍̂R񎦍זEᇍזEɔPD-L1邢PD-L2TזEɂ銈̗}ɒSIȑ݂łPD-1Ƃ̑ݍpՒfCTזE̊}Ȃ悤ɂpD

<h2>2Dɂh̖ƉuזEɂĎƎᇍזEɂƉủ</h2>
@ᇍזEBߒɂĂ͂܂܂Ȉ`qψق~ςDψقɂƂƏhɂ݂͑Ȃ^pNꍇ́CƉuזECȂłi`L[זEȂǎRƉun̖ƉuזEɔFj󂳂ƍlD̎ᇍזE̔j󂩂瓾ꂽ񎩌ȂƂĂ̍Ȑ́CɎזEɂ荞܂CRᇍזE̔inƂȂ郊p߂ւƓ`BDp߂ɂĂ͔񎩌Ȃ̍RɊւ͎זETזEւƓ`BC̍RٓIɔjł悤TזEBᇂւƍUߍłDŏIIɁCᇍזEƑΛTזE͎ᇂ̂ȐFj󂷂i<a href="#F2">}2a</a>jD̂悤ȖƉúCCᇂƂɂ͂܂@\Ƒz肳邪CᇍזEXɑBCƉu}悤ȉtq̕CƉu}̍זE̕CGlM[̍ȂǁCƉu邳܂܂ȋ@\l邱ƂɂCȖƉuj]Ƃߒz肳<a href="#R8"><sup>8)</sup></a>i<a href="#F2">}2b</a>j

<a name="F2"></a><div id="fig2-caption-text" style="display: none;"><strong>}2@h̖ƉuזEɂĎƎᇍזEɂƉủ</strong>
iajh̖ƉuזE͖Ɖủ̕ߒɂᇍזED
ibjᇍזE͕̋@\ɂƉuD
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2018/05/Koyama-7.e004-Fig.2.jpg" target="_blank">[Download]</a></div>[hs_figure id=2&amp;image=/wordpress/wp-content/uploads/2018/05/Koyama-7.e004-Fig.2.png&amp;caption=fig2-caption-text]

@̖Ɖu\镡̉ߒɂāCTזE̊}Ɖu`FbN|Cg^pN̂CƂPD-1PD-L1邢PD-L2Ƃ̑ݍpՒf邱ƂƉű@\̉񕜂̍ƂĂ͂炭Ƃ炩ɂꂽi<a href="#F3">}3</a>jDƉu`FbN|CgjQ͑K͂ȗՏɂėLꂽŏ̂ƉuÖ@ł͂̂́C񏬍זExɑ΂Ă͑Ŝ20`30ɌʂF߂݂̂ł邱ƂCƉu\RPD-1R̂̍p_̂قɂœ_ĂKvD܂CƉu`FbN|CgjQ򂪌ʂȂƉủ̋@\̕Dʂɋ@\Ă悤ȂɂẮCRPD-1R̂̒PƂɂ鎡Âɂʂ𓾂̂͂ނĈ悤ȔwiϐɊ֗^\lD

<a name="F3"></a><div id="fig3-caption-text" style="display: none;"><strong>}3@RPD-1R̂ɂ鎡ÂɂƉu͕Iɉ񕜂</strong>
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2018/05/Koyama-7.e004-Fig.3.jpg" target="_blank">[Download]</a></div>[hs_figure id=3&amp;image=/wordpress/wp-content/uploads/2018/05/Koyama-7.e004-Fig.3.png&amp;caption=fig3-caption-text]


<h2>3DRPD-1R̂邢͍RPD-L1R̂ɂ鎡Âɑ΂鏉ϐъlϐ</h2>
@񏬍זExɑ΂2ÂƂĂ̍RPD-1R̂̒PƂɂ鎡ẤCՏɂĂ͕WIȍR܂ɂ鎡ÂƔrĂ荂LĂ̂́CᇂƂ̑傫傫ȂȂԂێ閳ԂɂāCNXI[o[ƂIȐȐP[X񍐂Ă<a href="#R9"><sup>9)</sup></a>i<a href="#F4">}4</a>jD܂CꕔɂƉuÖ@ɂ܂ʂ̂Ȃ҂݂CŁCR܂ɂ鎡ÂɂĂ͍pキĂ薞ՂȂʂ邽߁C̒iKł͌ʂt]邱ƂD́CŏɂƉuÖ@I҂́CR܂ɂ鎡ÂIꍇƔrĕsvނ邱Ƃ̂\ĂĈ悤ȔwiCƉuÖ@ɑ΂銴󐫂邢͔񊴎󐫂炩߂݂߂悤ȃoCI}[J[̕KvꂽD܂ŁČO[vɂCƉuÖ@Ɋ󐫂̍҂𒊏o邽߂̃oCI}[J[ƂāCᇍזEɂPD-L1̔<a href="#R10"><sup>10)</sup></a>Cᇂɂ`qψق̗<a href="#R6"><sup>6)</sup></a>CɗVĂ郊p<a href="#R11"><sup>11)</sup></a>CȂǂ̗LpĂDƂ΁CPD-L1ᇂɂ`qψق̗ʂ傫񏬍זEx̊҂Ɍ肷ƁCRPD-1R̂ɂt75܂ŏ㏸邱Ƃꂽ<a href="#R5"><sup>5)</sup></a>DoCI}[J[̒lႢᇂɊւẮCƉuזE̍Rᇊ̂̂Ⴂ󋵁C܂CƂƍRPD-1R̂ɑ΂󐫂ȂϐɊ֗^邱ƂꂽD

<a name="F4"></a><div id="fig4-caption-text" style="display: none;"><strong>}4@RPD-1R̂ɂ鎡Âɑ΂鏉ϐъlϐ̏o鎞ԓIȉߒ</strong>
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2018/05/Koyama-7.e004-Fig.4.jpg" target="_blank">[Download]</a></div>[hs_figure id=4&amp;image=/wordpress/wp-content/uploads/2018/05/Koyama-7.e004-Fig.4.png&amp;caption=fig4-caption-text]

@܂ŁCᇍזȆSGL\V[NGXɂƂÂᇂɂ`qψق̗ʂvt@COĂ<a href="#R5"><sup>5)</sup></a>Cŋ߂̌їՏĈȂłRPD-1R̂ɑ΂銴󐫂ɂ`q肷邱Ƃ\ɂȂC̈`qψقɏœ_ĂčRPD-1R̂ɑ΂銴󐫂\邱Ƃ\ɂȂ<a href="#R12"><sup>12)</sup></a>D̊󐫈`qɂ<em>EGFR</em>`q<em>SKT11</em>`qȂǂ܂܂CM҂́C<em>Stk11</em>`q̌^ψق<em>Kras</em>x񃂃f}EXp͂ɂCƉuÖ@ɂ銴󐫂̒ቺ̌ƂāCᇂւ̃p̗V̒ቺCсCPD-L1̔̒ቺ֗^邱Ƃ<a href="#R13"><sup>13)</sup></a>DȊOɂCh̖ƉuזËqƂHLANXÏ`q^<a href="#R14"><sup>14)</sup></a> ⒰׋ۂ̃vt@C<a href="#R15"><sup>15)</sup></a> ϐɊ֗^邱ƂCᇍזËqƂĎᇂ̐ۉ<a href="#R16"><sup>16)</sup></a> 󐫂Ɋ֌W邱ƂŖ炩ɂꂽD
@ŁCɂ͎Â̌ʂĂɂ炸Cʂʂ̑gDɎᇂ̍đ𐶂P[XȂ炸݂悤ɂȂD̂悤ȎÂ̌ʂ̏̋@͊lϐƒ`CᇍזEяh̖ƉuזEɂĂx̎ԂĐK̕ωƁCᇍזEVȈ`qψقlĂƉuÖ@ɑ΂܂󐫂ȂȂω2ނɕĂƂ炦邱Ƃł<a href="#R17"><sup>17)</sup></a>DRPD-1R̂ɑ΂lϐ́C̎gp̑ɂƂÂۂ̗ՏɂĂ΂Όo悤ɂȂĂD

<h2>4DᇍזEɂ`qψق̊lɂƂȂlϐ</h2>
@RPD-1R̂̒̎gpႪȂŁC͎ᇍזEɑ΂RPD-1R̂ʂɂ炸ĈɎᇂđ債ĂǗႪ΂Όo悤ɂȂDÑOэđ厞̎ᇑgD̎悵`qvt@Cr邱ƂɂCᇍזEVȈ`qψقl邱ƂɂRPD-1R̂ɑ΂ϐl邱Ƃ񏥂ꂽ<a href="#R18"><sup>18)</sup></a>ĎɂẮC畆̊҂̂RPD-1R̂rŌȂȂǗɂāCRPD-1R̂̎gpOъlϐô̓̕ʂ̎ᇑgD`wIɔrCJAK1/JAK2-STAT1VOi`Bn邢̓2~NOuɐVɕψقǗႪ񎦂ꂽD̈`qψقɂCᇍזEɂĂƂ傫ω͍̂R񎦔\łD񎩌ȂFh̖ƉuɂCƂTזEɂĎYC^[tF́CRᇊ̔ɂĒSIȖ͂łȂCᇍזEɂPD-L1MHCNXIq̗̔UɂĂ傫Ȍ͂ƂȂDRPD-1R̂ɂPD-L1ɂ}ȂȂTזE̓C^[tFYDʏ́C̋@\ɂWIƂȂᇍזEɂčR񎦂𑣐iRᇌʂ₷邪ClϐЂN悤Ȉ`q̕ψقƂȂᇍזEɂĂ̓C^[tF̃VOi`Bn܂@\ȂȂ邱ƂɂCᇍזEꎩ̂̍R񎦔\QCTזEᇍזEFłȂȂD܂CȂ͂̌ʁCRPD-1R̂ɂ鎡Â̂܂Ĉ悤ȃC^[tFɊ֘AVOi`Bnɂ`qψق<em>de novo</em>ψقƂĂᇂ܂ɑ݂Ĉ悤ȏꍇ͍RPD-1R̂ɑ΂ϐ<a href="#R19"><sup>19)</sup></a>D܂Cl̊lϐ̋@͔x̊҂ɂĂώ@ꂽ<a href="#R20"><sup>20)</sup></a>Dȏ̂悤ɁClϐ̋@͂邱Ƃ́CVȏϐ̋@𗝉邱ƂɂȂ邱ƂꂽD̂悤Ȃɑ΂Ă͂ǂ̂悤ȎÂD悳ׂC̏dvȌۑłD

<h2>5DƉuזE̕ωɂƂȂlϐ</h2>
@RPD-1R̂ɂ鎡Â̍p_͏hTזEłCᇍזEłȂCh̖ƉuזȆ̗vłϐ̐\ꂽDM҂́Cᇂɂlϐ񍐂ȑOɁCTזEɂ̈q̕ωɂRPD-1R̂ɂ鎡Â̌ʂᇂđ傷Ǘɂĕ񍐂<a href="#R21"><sup>21)</sup></a>DTזE̕\ʂɂ͕̖Ɖu`FbN|Cg^pN݂CTזEɂĂPD-1̂قɂCTLA-4CTIM-3CLAG3Ȃǂ邱ƂmĂDx񃂃f}EXɂāCCRPD-1R̂Ɋ󐫂ᇂđ債Ă錻ۂɒڂCÂĂȂᇂTזEƊlϐᇂTזEƂrƂCPD-1̂ق̖̕Ɖu`FbN|Cg^pN̔Lӂɏ㏸ĂDƂTIM-3̔㏸ĂClϐ_ōRTIM-3R̂̕pJnƁCꎞIɂł͂邪ӂюÂ̌ʂF߂ꂽ<a href="#R21"><sup>21)</sup></a>D̂悤ɁCRPD-1R̂̒̎gpɂCÑOɂ͕s邢͍זENĂTזE蒷C̈ꕔ͂芈邢͂敾ԂŌoꂽƂC܂܂ȖƉu`FbN|Cg^pN̔͘iDPD-1̂ق̖Ɖu`FbN|Cg^pÑKh͂ɂĂ͈ʓIɌô߁CRPD-1R̂TזEɂĂɂeՂɗ}邱ƂꂽD
@̂悤ɁCᇍזEƂ͓ƗTזẼvt@CXɕω邱ƂɂPD-1̑jQ̌ʂシߒlϐɊ^ĂƂĈ悤ȊlϐK̑ϐƖÂ<a href="#R17"><sup>17,21)</sup></a>Dɂ킽RPD-1R̂̎gp̂̂ɍĔ2SXыCɑ݂TזEmFƂCRPD-1R̂܂ĂTזETIM-3ĂD܂CTIM-3̃KhƂĒmĂKN`9̑̍otɂZx́CRPD-1R̂ɂ莡ÂĂȂ҂̋ƔrČɍȂĂDKN`9PD-L1MHCNXIqƓlɃC^[tFVOi`Bnɂ蔭U邱ƂmĂ<a href="#R22"><sup>22)</sup></a>CTזÊu[Ln̂̂ƉuÖ@ɂĂ͊lϐɊ^\ꂽDM҂̌ɂÂĈ悤TזE̓̊lϐ̋@葽̏ǗɂĎĂ<a href="#R20"><sup>20)</sup></a>D

<h2></h2>
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<h2> </h2>
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</ol>
<div class="au-profile">
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<span class="author">R iShohei Koyamaj</span>
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