I-Immunotherapy ilethe izinguquko eziguquguqukayo ekwelapheni izimila eziyingozi, kodwa kuseneziguli ezingakwazi ukuzuza. Ngakho-ke, ama-biomarker afanelekile adingeka ngokushesha ekusetshenzisweni komtholampilo ukuze abikezele ukusebenza kahle kwe-immunotherapy, ukuze kwandiswe ukusebenza kahle futhi kugwenywe ubuthi obungadingekile.
I-FDA igunyaze ama-biomarker
Inkulumo ye-PD-L1. Ukuhlolwa kwamazinga okuvezwa kwe-PD-L1 nge-immunohistochemistry (IHC) kuveza i-tumor proportion score (TPS), okuyiphesenti ingxenye noma ngokuphelele yamaseli esimila esinamabala anolwelwesi lwanoma ibuphi ukuqina kumaseli wesimila asindayo. Ezivivinyweni zomtholampilo, lokhu kuhlola kusebenza njengokuhlola okuyisizayo kokwelashwa komdlavuza wamaphaphu ongewona omncane wengqamuzana (NSCLC) nge-pembrolizumab. Uma i-TPS yesampula ingu-≥ 1%, isisho se-PD-L1 siyacatshangelwa; I-TPS ≥ 50% ibonisa ukuvezwa okuphezulu kwe-PD-L1. Esivivinyweni sokuqala seSigaba 1 (KEYNOTE-001), izinga lokuphendula leziguli ku-PD-L1 TPS>50% yeqembu elincane elisebenzisa i-pembrolizumab lalingu-45.2%, kuyilapho kungakhathaliseki ukuthi i-TPS, izinga lokuphendula lazo zonke iziguli ezithola le mithi yokwelapha i-immune checkpoint inhibitor (ICI) yayingu-19.4%. Isivivinyo esilandelayo sesigaba sesi-2/3 (KEYNOTE-024) sabela ngokungahleliwe iziguli ezine-PD-L1 TPS>50% ukuze zithole i-pembrolizumab kanye ne-chemotherapy evamile, futhi imiphumela yabonisa ukuthuthuka okuphawulekayo ekusindeni okuphelele (OS) ezigulini ezithola ukwelashwa kwe-pembrolizumab.
Nokho, ukusetshenziswa kwe-PD-L1 ekubikezeleni izimpendulo ze-ICI kunqunyelwe izici ezihlukahlukene. Okokuqala, umkhawulo ofanele wezinhlobo ezahlukene zomdlavuza uyahluka. Isibonelo, i-Pabolizumab ingasetshenziswa lapho isimila se-PD-L1 seziguli ezinomdlavuza wesisu, umdlavuza we-esophageal, umdlavuza wesinye kanye nomdlavuza wamaphaphu kungu-1%, u-10% no-50% ngokulandelanayo. Okwesibili, ukuhlola inani lamaseli wenkulumo ye-PD-L1 kuyahlukahluka kuye ngohlobo lomdlavuza. Isibonelo, ukwelashwa kwe-squamous cell carcinoma ephindaphindiwe noma ye-metastatic yekhanda nentamo ingase ikhethe ukusebenzisa enye indlela yokuhlola evunyelwe yi-FDA, i-Comprehensive Positive Score (CPS). Okwesithathu, cishe akukho ukuhlobana phakathi kwenkulumo ye-PD-L1 kumdlavuza ohlukahlukene kanye nokuphendula kwe-ICI, okubonisa ukuthi isizinda sesimila singaba yisici esibalulekile ekubikezeleni ama-biomarker e-ICI. Isibonelo, ngokwemiphumela yokuhlolwa kwe-CheckMate-067, inani elibi lokubikezela le-PD-L1 inkulumo ku-melanoma lingama-45% kuphela. Ekugcineni, izifundo eziningi zithole ukuthi isisho se-PD-L1 asihambisani kuzo zonke izilonda zesimila esigulini esisodwa, ngisho nangaphakathi kwesimila esifanayo. Kafushane, yize izivivinyo zokuqala zomtholampilo ze-NSCLC zenze ucwaningo ngesisho se-PD-L1 njengesibikezelo se-biomarker esingaba khona, ukusetshenziswa kwayo emitholampilo ezinhlotsheni ezahlukene zomdlavuza kusalokhu kungacaci.
Umthwalo wokuguqula i-tumor. I-Tumor Mutation Burden (TMB) isetshenziswe njengenye inkomba ye-tumor immunogenicity. Ngokwemiphumela yokuhlolwa komtholampilo ye-KEYNOTE-158, phakathi kwezinhlobo ezingu-10 zamathumba aqinile athuthukile alashwa nge-pembrolizumab, iziguli ezinokuguqulwa okungenani okungu-10 nge-megabase ngayinye (i-TMB ephezulu) zinezinga lokuphendula eliphezulu kunalezo ezine-TMB ephansi. Kuyaphawuleka ukuthi kulolu cwaningo, i-TMB ibiyisibikezelo se-PFS, kodwa ayikwazanga ukubikezela i-OS.
Ukusabela kwe-immune therapy kuqhutshwa ngokuyinhloko ukuqashelwa kwe-T cell yama-antigen amasha. I-immunogenicity ehlotshaniswa ne-TMB ephakeme nayo incike ezicini ezihlukahlukene, kuhlanganise ne-tumor neoantigen ethulwa yisimila; Amasosha omzimba aqaphela ama-neoantigens wesimila; Ikhono lomsingathi ukuqalisa izimpendulo eziqondene ne-antigen. Isibonelo, idatha iphakamisa ukuthi izimila ezinokungena okuphezulu kakhulu kwamanye amaseli omzimba angase abe nokukhuliswa kwe-clone kwe-T cell (Treg) elawulayo evimbelayo. Ukwengeza, ububanzi be-TMB bungase buhluke emandleni e-TMB neoantigens, njengoba indawo okuyiyonayona yokuguqulwa kwezakhi zofuzo nayo idlala indima ebalulekile; Uguquko oluxhumanisa izindlela ezihlukene zokwethulwa kwe-antigen lungathinta ukwethulwa (noma okungeyona iphrezentheshini) yama-antigen amasha ohlelweni lokuzivikela komzimba, okubonisa ukuthi izici ze-tumor intrinsic kanye ne-immunological kumele zihambisane ukuze kukhiqizwe izimpendulo ezilungile ze-ICI.
Njengamanje, i-TMB ikalwa ngokusebenzisa ukulandelana kwesizukulwane esilandelayo (NGS), okungase kwehluke ezikhungweni ezahlukene (ngaphakathi) noma izinkundla zentengiso ezisetshenziswayo. I-NGS ihlanganisa ukulandelana okuphelele kwe-exome (WES), ukulandelana kwe-genome okuphelele, nokulandelana okuhlosiwe, okungatholakala kuzicubu zesimila kanye ne-circulating tumor DNA (ctDNA). Kuyaphawuleka ukuthi izinhlobo ezahlukene zezimila zinezinhlobonhlobo ze-TMB, ezinamathumba avikela umzimba kumasosha omzimba njengemelanoma, i-NSCLC, kanye ne-squamous cell carcinoma enamazinga aphezulu e-TMB. Ngokufanayo, izindlela zokuthola ezidizayinelwe izinhlobo ezihlukene zesimila zinezincazelo ezihlukile zamavelu we-TMB threshold. Ocwaningweni lwe-NSCLC, i-melanoma, i-urothelial carcinoma, nomdlavuza wamangqamuzana amancane wamaphaphu, lezi zindlela zokuthola zisebenzisa izindlela zokuhlaziya ezihlukene (ezifana nokutholwa kwe-WES noma i-PCR ngezinombolo ezithile zezakhi zofuzo ezihlobene) kanye nama-threshold (i-TMB ephezulu noma i-TMB ephansi).
Amasathelayithi amancane azinzile kakhulu. I-Microsatellite engazinzile kakhulu (MSI-H), njenge-pan cancer biomarker ye-ICI impendulo, inokusebenza okuhle kakhulu ekubikezeleni ukusebenza kwe-ICI kumdlavuza ohlukahlukene. I-MSI-H iwumphumela wokukhubazeka kokulungisa okungafani (dMMR), okuholela ekuguquguqukeni okuphezulu, ikakhulukazi ezindaweni ezincane ze-microsatellite, okuholela ekukhiqizweni kwenani elikhulu lama-antigen amasha futhi ekugcineni kubangele ukusabela komzimba we-clonal. Ngenxa yomthwalo omkhulu wokuguqula owenziwe i-dMMR, izimila ze-MSI-H zingabhekwa njengohlobo lomthwalo omkhulu wokuguqula (TMB) isimila. Ngokusekelwe emiphumeleni yokuhlolwa komtholampilo ye-KEYNOTE-164 kanye ne-KEYNOTE-158, i-FDA igunyaze i-pembrolizumab yokwelashwa kwe-MSI-H noma izimila ze-dMMR. Lona omunye wemithi yokuqala yomdlavuza we-pan egunyazwe yi-FDA eqhutshwa yi-tumor biology kune-histology.
Naphezu kwempumelelo enkulu, kukhona nezinkinga okufanele uziqaphele lapho usebenzisa isimo se-MSI. Isibonelo, kufika ku-50% weziguli ezinomdlavuza we-dMMR ongenazo impendulo ekwelashweni kwe-ICI, okugqamisa ukubaluleka kwezinye izici ekubikezeleni impendulo. Ezinye izici zangaphakathi zamathumba ezingakwazi ukuhlolwa yizinkundla zokutholwa zamanje zingase zibe nomthelela. Isibonelo, kube nemibiko yokuthi iziguli ezinokuguqulwa kofuzo ezifaka amayunithi abalulekile e-catalytic we-polymerase delta (POLD) noma i-polymerase ε (POLE) esifundeni se-DNA azinakho ukwethembeka kokuphindaphinda futhi zibonisa i-phenotype "yenguquko ephezulu" kumathumba azo. Amanye alawa mathumba akhulise kakhulu ukungazinzi kwe-microsatellite (ngaleyo ndlela engeye-MSI-H), kodwa amaprotheni okulungisa ukungafani awantuli (ngakho-ke awekho i-dMMR).
Ukwengeza, efana ne-TMB, i-MSI-H iphinde ithinteke yizinhlobo ezintsha ze-antigen ezikhiqizwa ukungazinzi kwe-microsatellite, ukuqashelwa komphathi wezinhlobo ezintsha ze-antigen, kanye nokusabela kwesistimu yomzimba yokuzivikela. Ngisho nakumathumba ohlobo lwe-MSI-H, inombolo enkulu yokuguqulwa kwe-nucleotide eyodwa ikhonjwe njengokuguquguquka kwabagibeli (ukuguqulwa okungezona umshayeli). Ngakho-ke, ukuthembela kuphela enanini lama-microsatellites akhonjwe esimila akwanele; Uhlobo lwangempela lokuguqulwa (okukhonjwe ngamaphrofayili athile okuguqula) lungathuthukisa ukusebenza okuqagelayo kwalesi sikhombisi sezinto eziphilayo. Ngaphezu kwalokho, ingxenye encane kuphela yeziguli ezinomdlavuza ezingamalungu e-MSI-H tumors, okubonisa isidingo samanje sama-biomarker asebenza kabanzi. Ngakho-ke, ukuhlonza amanye ama-biomarker asebenzayo ukubikezela ukusebenza kahle nokuqondisa ukuphathwa kwesiguli kuhlala kuyindawo ebalulekile yocwaningo.
Ucwaningo lwe-biomarker olusekelwe enhlanganweni
Njengoba kunikezwe ukuthi indlela yokusebenza ye-ICI iwukuhlehlisa ukucindezelwa kwamangqamuzana omzimba kunokuba iqondise ngokuqondile izindlela zangaphakathi zamangqamuzana ethumba, ucwaningo olwengeziwe kufanele lugxile ekuhlaziyeni ngokuhlelekile indawo yokukhula kwesimila kanye nokusebenzelana phakathi kwamaseli wesimila namaseli omzimba, okungasiza ukucacisa izici ezithinta impendulo ye-ICI. Amaqembu amaningi ocwaningo afunde izimila noma izici zokuzivikela komzimba zezinhlobo ezithile zezicubu, njengezimila nezici zokuguqula izakhi zofuzo, ukushoda kwesethulo se-tumor antigen, noma izikhungo zokuzivikela ezifweni eziningi noma amaqoqo (njengezakhiwo ze-lymphoid ephakeme), ezingabikezela izimpendulo ku-immunotherapy.
Abacwaningi basebenzise i-NGS ukulandelana kwe-tumor kanye ne-immune exome kanye ne-transcriptome yezicubu zesiguli ngaphambi nangemuva kokwelashwa kwe-ICI, futhi benza ukuhlaziywa kwe-spatial imaging. Ngokusebenzisa amamodeli amaningi ahlanganisiwe, ahlanganiswe namasu afana nokulandelana kweseli elilodwa kanye nesithombe sendawo, noma amamodeli we-multi omics, ikhono lokubikezela lemiphumela yokwelapha ye-ICI lithuthukisiwe. Ngaphezu kwalokho, indlela ebanzi yokuhlola izimpawu zokuzivikela sisimila kanye nezici zesimila esingaphakathi nayo ibonise amandla okuqagela anamandla. Isibonelo, indlela ebanzi yokulandelana kwenqwaba ekala ngasikhathi sinye isimila kanye nezici zokuzivikela komzimba iphakeme kunokuhluka okukodwa kokuhlaziya. Le miphumela iqokomisa isidingo sokulingisa ukusebenza kwe-ICI ngendlela ebanzi, okuhlanganisa nokuhlanganisa imiphumela yokuhlola yamandla okuzivikela omzimba aphethe, izici zesimila sangaphakathi, kanye nezingxenye zokuzivikela zesimila esigulini ngasinye ukubikezela kangcono ukuthi yiziphi iziguli ezizosabela ku-immunotherapy.
Uma kubhekwa inkimbinkimbi yokufaka isimila kanye nezici zokubamba ocwaningweni lwe-biomarker, kanye nesidingo esingaba khona sokuhlanganiswa kwesikhathi eside kwezici ze-immune microenvironment, abantu sebeqalile ukuhlola ama-biomarker besebenzisa imodeli yekhompyutha nokufunda komshini. Njengamanje, ezinye izimpumelelo zocwaningo eziphusile sezivele kulo mkhakha, okukhombisa ikusasa le-oncology yomuntu siqu esizwa ukufunda ngomshini.
Izinselelo ezibhekene nama-biomarker asuselwa kuzicubu
Imikhawulo yezindlela zokuhlaziya. Amanye ama-biomarker anengqondo enza kahle ezinhlotsheni ezithile zesimila, kodwa hhayi kwezinye izinhlobo zesimila. Nakuba izici zofuzo ezithile zesimila zinamandla okubikezela anamandla kune-TMB nezinye, azikwazi ukusetshenziselwa ukuxilonga zonke izimila. Ocwaningweni oluqondiswe ezigulini ze-NSCLC, izici zokuguqula izakhi zofuzo zitholwe zibikezela kakhulu ukusebenza kwe-ICI kune-TMB ephezulu (≥ 10), kodwa ngaphezu kwesigamu seziguli azikwazanga ukuthola izici zokuguqulwa kofuzo.
I-Tumor heterogeneity. Indlela ye-biomarker yezicubu esekelwe kumasampula kuphela endaweni eyodwa yesimila, okusho ukuthi ukuhlolwa kwezingxenye ezithile zesimila kungase kungabonisi ngokunembile ukuvezwa kwawo wonke amathumba esigulini. Isibonelo, izifundo zithole ukuhlukahluka ekukhulumeni kwe-PD-L1 phakathi nangaphakathi kwamathumba, futhi izinkinga ezifanayo zikhona ngezinye izimpawu zethishu.
Ngenxa yobunkimbinkimbi bezinhlelo zebhayoloji, ama-biomarker amaningi wezicubu asetshenziswe ngaphambilini kungenzeka enziwe aba lula ngokweqile. Ngaphezu kwalokho, amaseli ku-tumor microenvironment (TME) ngokuvamile ayahamba, ngakho ukusebenzisana okuboniswa ekuhlaziyweni kwendawo kungase kungameleli ukusebenzisana kwangempela phakathi kwamaseli wesimila namaseli omzimba. Ngisho noma ama-biomarker angamelela kahle yonke indawo yesimila ngesikhathi esithile, lezi zinhloso zisenganxenxwa futhi zishintshe ngokushintshashintshayo ngokuhamba kwesikhathi, okubonisa ukuthi isifinyezo esisodwa ngesikhathi singase singameli izinguquko eziguquguqukayo kahle.
I-heterogeneity yesiguli. Ngisho noma izinguquko zofuzo ezaziwayo ezihlobene nokumelana ne-ICI zitholwa, ezinye iziguli eziphethe izimpawu zezinto eziphilayo ezaziwayo zingase zizuze, mhlawumbe ngenxa ye-molecular and/noma immune heterogeneity ngaphakathi kwesimila nasezindaweni ezihlukene zesimila. Isibonelo, ukushoda kwe-β 2-microglobulin (B2M) kungase kubonise ukuphikiswa kwezidakamizwa okusha noma okutholiwe, kodwa ngenxa yokuhlukahluka kokuntuleka kwe-B2M phakathi kwabantu ngabanye nangaphakathi kwamathumba, kanye nokusebenzisana kwezindlela zokushintshwa kokuqashelwa kwamasosha omzimba kulezi ziguli, ukuntula kwe-B2M kungase kungabikezeli ngokuqinile ukumelana nemithi ngayinye. Ngakho-ke, naphezu kokuba khona kokuntuleka kwe-B2M, iziguli zisengazuza ekwelashweni kwe-ICI.
Ama-biomarker we-longitudinal asuselwa kunhlangano
Ukuvezwa kwama-biomarker kungashintsha ngokuhamba kwesikhathi kanye nomthelela wokwelashwa. Ukuhlolwa okuqinile nokukodwa kwamathumba kanye ne-immunobiology kungase kunganaki lezi zinguquko, futhi izinguquko ku-TME yesimila kanye namazinga okuphendula amasosha omzimba angase anganakwa. Ucwaningo oluningi lubonise ukuthi ukuthola amasampula ngaphambi nangesikhathi sokwelashwa kungakwazi ukubona ngokunembile izinguquko ezihlobene nokwelashwa kwe-ICI. Lokhu kugqamisa ukubaluleka kokuhlolwa kwe-biomarker enamandla.
Ama-biomarker asekelwe egazini
Inzuzo yokuhlaziywa kwegazi ilele emandleni alo okuhlola ngokwebhayoloji zonke izilonda zesimila ngazinye, ebonisa ukufundwa okumaphakathi kunokufundwa kwesayithi okuthile, okulenza lifaneleke ngokukhethekile ukuhlola izinguquko eziguquguqukayo ezihlobene nokwelashwa. Imiphumela eminingi yocwaningo ibonise ukuthi ukusebenzisa i-circulating tumor DNA (ctDNA) noma circulating tumor cell (CTC) ukuhlola isifo esincane esisalayo (MRD) kungaqondisa izinqumo zokwelashwa, kodwa lokhu kuhlolwa kunolwazi olulinganiselwe lokubikezela ukuthi iziguli zingazuza yini kuma-immunotherapies afana ne-ICI. Ngakho-ke, ukuhlolwa kwe-ctDNA kudinga ukuhlanganiswa nezinye izindlela zokukala ukusebenza kokuzivikela komzimba noma amandla okuvikela amasosha omzimba. Mayelana nalokhu, inqubekelaphambili yenziwe ekuhlolweni kokuzivikela komzimba kwamangqamuzana egazi angama-peripheral mononuclear (PBMCs) kanye nokuhlaziywa kwe-proteomic yama-vesicles angaphandle kweseli kanye ne-plasma. Isibonelo, i-peripheral immune cell subtypes (njengamaseli e-CD8+T), ukubonakaliswa okuphezulu kwama-molecule e-immune checkpoint (afana ne-PD1 kumaseli we-CD8+T we-peripheral), kanye namazinga aphakeme amaprotheni ahlukahlukene ku-plasma (njenge-CXCL8, CXCL10, IL-6, IL-10, PRAP1, kanye ne-VEGDNA esebenzayo ye-biodynamics ingase isebenze njenge-biodynamics ye-VEGFA). Inzuzo yalezi zindlela ezintsha ukuthi zingahlola izinguquko ngaphakathi kwesimila (ezifana nezinguquko ezitholwe yi-ctDNA) futhi zingase zembule izinguquko kumasosha omzimba esiguli.
Ama-radiomics
Izinto eziqagelayo zedatha yesithombe zinganqoba ngempumelelo imikhawulo yesampula ye-biomarker yezicubu kanye ne-biopsy, futhi zingakwazi ukubona isimila kanye nezinye izingosi ze-metastatic nganoma yisiphi isikhathi. Ngakho-ke, bangase babe yingxenye ebalulekile yama-biomarker ashukumisayo angavaleli esikhathini esizayo. I-Delta radiomics ingakwazi ukubala ngobuningi izinguquko ezicini eziningi zesimila (ezifana nosayizi wesimila) ngezikhathi ezihlukene, njengangaphambi nangemuva kokwelashwa kwe-ICI, phakathi nokwelashwa, kanye nokulandelela okulandelayo. I-Delta radiomics ayikwazi nje ukubikezela impendulo yokuqala noma engekho ekwelashweni kwangaphambi kwesikhathi, kodwa futhi ihlonze ukumelana okutholwe ku-ICI ngesikhathi sangempela futhi iqaphe noma yikuphi ukuphindeka ngemva kokuxolelwa okuphelele. Imodeli yokuthwebula ethuthukiswe ngobuchwepheshe bokufunda komshini ingcono nakakhulu kunezinga le-RECIST elivamile lokubikezela impendulo yokwelashwa kanye nezenzakalo ezimbi ezingaba khona. Ucwaningo lwamanje lubonisa ukuthi lezi zinhlobo zama-radiomics zinendawo engaphansi kwejika (AUC) efika ku-0.8 kuye ku-0.92 ekubikezeleni impendulo yokwelashwa komzimba.
Enye inzuzo yama-radiomics yikhono layo lokukhomba ngokunembile ukuqhubeka kwe-pseudo. Imodeli yama-radiomics eyakhiwe ngokufunda komshini ingahlukanisa ngempumelelo phakathi kokuqhubeka kweqiniso nokungamanga ngokulinganisa kabusha idatha ye-CT noma ye-PET yesimila ngasinye, okuhlanganisa izici ezifana nokuma, ukuqina, nokuthungwa, nge-AUC engu-0.79. Lawa mamodeli e-radiomics angasetshenziswa esikhathini esizayo ukuze agweme ukunqanyulwa kokwelashwa ngaphambi kwesikhathi ngenxa yokungahluleli kahle kokuqhubeka kwesifo.
I-microbiota yamathumbu
Ama-biomarker we-gut microbiota kulindeleke ukuthi abikezele impendulo yokwelapha ye-ICI. Ucwaningo oluningi lubonise ukuthi i-gut microbiota ethile ihlobene eduze nokusabela kwezinhlobo ezahlukene zomdlavuza ekwelashweni kwe-ICI. Isibonelo, ezigulini ezinomdlavuza we-melanoma nesibindi, ukuchichima kwebhaktheriya ye-Ruminococcaceae kuhlotshaniswa nempendulo ye-PD-1 immunotherapy. Ukucebisa kwe-Akkermansia muciniphila kuvamile ezigulini ezinomdlavuza wesibindi, umdlavuza wamaphaphu, noma i-renal cell carcinoma, ezisabela kahle ekwelashweni kwe-ICI.
Ngaphezu kwalokho, imodeli entsha yokufunda yomshini ingazimele ezinhlotsheni zesimila futhi ihlobanise uhlobo oluthile lwebhaktheriya yamathumbu kanye nokusabela kokwelapha kwe-immunotherapy. Olunye ucwaningo luphinde lwembula indima ethile edlalwa amaqembu ebhaktheriya ngamanye ekulawuleni amasosha omzimba, ngokuqhubeka nokuhlola ukuthi angavinjwa kanjani noma akhuthaze ukuphuma komzimba kumaseli omdlavuza.
Ukwelashwa kwe-Neoadjuvant
Ukuhlolwa okunamandla kwebhayoloji yesimila kungaqondisa amasu okwelashwa alandelayo. Isilingo sokwelashwa kwe-neoadjuvant singahlola umphumela wokwelapha ngokukhululeka kokugula ezinhlotsheni zokuhlinzwa. Ekwelapheni i-melanoma, impendulo eyinhloko ye-pathological (MPR) ihlotshaniswa nesilinganiso sokusinda samahhala sokuphindaphinda. Esivivinyweni se-PRADO, abacwaningi banquma izinyathelo ezilandelayo zokungenelela emtholampilo, ezifana nokuhlinzwa kanye/noma ukwelashwa kwe-adjuvant, ngokusekelwe kudatha yesiguli ethile yokukhululwa kwe-pathological.
Phakathi kwezinhlobo ezahlukene zomdlavuza, izinketho eziningi ezintsha zokwelapha i-adjuvant zisantula ukuqhathaniswa kwekhanda nekhanda. Ngakho-ke, ukukhetha phakathi kwe-immunotherapy monotherapy noma ukwelashwa okuhlangene kuvame ukunqunywa ngokuhlanganyela ngudokotela okhona kanye nesiguli. Njengamanje, abacwaningi benze isici se-interferon gamma (IFN gamma) esiqukethe izakhi zofuzo eziyi-10 njenge-biomarker yokubikezela ukukhululwa kwe-pathological ku-melanoma ngemva kokwelashwa kwe-neoadjuvant. Baphinde bahlanganisa lezi zici ku-algorithm yokukhetha iziguli ezinezimpendulo eziqinile noma ezibuthakathaka ekwelashweni kwe-neoadjuvant. Ocwaningweni olulandelwayo olubizwa nge-DONIMI, abacwaningi basebenzise lesi sibalo, kuhlanganiswe nokuhlaziywa okuyinkimbinkimbi, hhayi nje ukubikezela impendulo yokwelashwa, kodwa futhi nokunquma ukuthi yisiphi isigaba se-III seziguli ze-melanoma ezidinga ukungezwa kwe-histone deacetylase inhibitors (HDACi) ukuze kuthuthukiswe impendulo ekwelashweni kwe-ICI ye-neoadjuvant.
Imodeli yesimila etholakala ezigulini
Amamodeli we-in vitro tumor anamandla okubikezela izimpendulo eziqondile zesiguli. Ngokungafani nenkundla ye-in vitro esetshenziselwa ukuhlaziya i-spectrum yokusabela kwezidakamizwa ye-hematological malignancies, izimila eziqinile zibhekana nezinselele ezinkulu ngenxa ye-microstructure yazo ehlukile yesimila kanye nokusebenzisana kokuzivikela komzimba kwesimila. Isiko leseli lesimila elilula alikwazi ukuphindaphinda kalula lezi zici eziyinkimbinkimbi. Kulokhu, isimila esifana nezitho noma izithonjana zesitho esivela ezigulini zinganxephezela le mikhawulo yesakhiwo, njengoba zingakwazi ukulondoloza ukwakheka kwamangqamuzana oqobo futhi zilingise ukusebenzisana namaseli e-lymphoid kanye ne-myeloid immune cell ukuhlola izimpendulo ze-ICI ngendlela ethize yesiguli, ngaleyo ndlela zikhiqize kabusha izici zebhayoloji ngokunembe kakhulu endaweni engokoqobo enezinhlangothi ezintathu.
Izifundo eziningi eziyimpumelelo e-China nase-United States zamukele le modeli entsha ye-high fidelity high-dimensional in vitro tumor. Imiphumela ibonisa ukuthi lawa mamodeli angabikezela ngempumelelo impendulo yomdlavuza wamaphaphu, umdlavuza wekoloni, umdlavuza webele, i-melanoma nezinye izimila ku-ICI. Lokhu kubeka isisekelo sokuqinisekisa okuqhubekayo kanye nokumisa ukusebenza okubikezelwayo kwalawa mamodeli.
Isikhathi sokuthumela: Jul-06-2024