iindaba

I-Immunotherapy izise utshintsho oluguquguqukayo kunyango lwamathumba anobungozi, kodwa kusekho izigulana ezingenakuzuza. Ke ngoko, ii-biomarkers ezifanelekileyo zifuneka ngokukhawuleza kwizicelo zeklinikhi ukuqikelela ukusebenza kwe-immunotherapy, ukuze kwandiswe ukusebenza kakuhle kwaye kuthintelwe ubuthi obungeyomfuneko.

I-FDA evunyiweyo i-biomarkers

PD-L1 intetho. Uvavanyo PD-L1 amanqanaba intetho yi immunohistochemistry (IHC) ivelisa ithumba umlinganiselo amanqaku (TPS), nto leyo ipesenti ngokuyinxenye okanye ngokupheleleyo inwebu iiseli ithumba stained nawuphi na ukuqina ezisindayo iiseli ithumba. Kulingo lwezonyango, olu vavanyo lusebenza njengovavanyo oluncedisayo lokuxilonga kunyango lomhlaza wemiphunga weseli ongekho mncinane (NSCLC) nge-pembrolizumab. Ukuba i-TPS yesampuli ≥ 1%, inkcazo ye-PD-L1 iqwalaselwa; I-TPS ≥ i-50% ibonisa ukubonakaliswa okuphezulu kwe-PD-L1. Kwinqanaba lokuqala leSigaba se-1 (KEYNOTE-001), izinga lokuphendula izigulane kwi-PD-L1 TPS> i-50% ye-subgroup esebenzisa i-pembrolizumab yayingu-45.2%, ngelixa kungakhathaliseki ukuba yi-TPS, izinga lokuphendula kuzo zonke izigulane ezifumana le nyango ye-immune checkpoint inhibitor (ICI) yayiyi-19.4%. Uvavanyo lwesigaba esilandelayo se-2 / 3 (KEYNOTE-024) izigulane ezibekwe ngokungaqhelekanga kunye ne-PD-L1 TPS> i-50% yokufumana i-pembrolizumab kunye ne-chemotherapy eqhelekileyo, kwaye iziphumo zibonise ukuphuculwa okuphawulekayo kwimpilo yonke (OS) kwizigulane ezifumana unyango lwe-pembrolizumab.

Nangona kunjalo, ukusetyenziswa kwe-PD-L1 ekuqikeleleni iimpendulo ze-ICI kukhawulelwe yimiba eyahlukeneyo. Okokuqala, umyinge ofanelekileyo weentlobo ezahlukeneyo zomhlaza uyahluka. Ngokomzekelo, i-Pabolizumab ingasetyenziswa xa i-tumor PD-L1 ibonakaliso yezigulane ezinomhlaza wesisu, umhlaza we-esophageal, umhlaza wesinyi kunye nomhlaza wemiphunga yi-1%, i-10% kunye ne-50% ngokulandelanayo. Okwesibini, ukuvavanya inani leseli ye-PD-L1 intetho iyahluka ngokuxhomekeke kuhlobo lomhlaza. Ngokomzekelo, unyango lwe-squamous cell carcinoma ephindaphindiweyo okanye i-metastatic yentloko kunye nentamo ingakhetha ukusebenzisa enye indlela yokuvavanya evunyiweyo ye-FDA, i-Comprehensive Positive Score (CPS). Okwesithathu, phantse akukho nxu lumano phakathi kwe-PD-L1 ukubonakaliswa kwiintlobo ezahlukeneyo zomhlaza kunye nempendulo ye-ICI, ebonisa ukuba imvelaphi ye-tumor inokuba yinto ephambili ekuqikeleleni i-ICI biomarkers. Ngokomzekelo, ngokweziphumo zovavanyo lwe-CheckMate-067, ixabiso elibi lokuxela kwangaphambili kwe-PD-L1 kwi-melanoma yi-45 kuphela. Okokugqibela, izifundo ezininzi ziye zafumanisa ukuba intetho ye-PD-L1 ayihambelani kwizilonda ezahlukeneyo zethumba kwisigulana esinye, nangaphakathi kwethumba elinye. Isishwankathelo, nangona ulingo lokuqala lweklinikhi lwe-NSCLC lukhuthaze uphando kwi-PD-L1 ibinzana njenge-biomarker enokwenzeka yokuqikelela, ukusetyenziswa kwayo kweklinikhi kwiintlobo ezahlukeneyo zomhlaza kuhlala kungacacanga.

Umthwalo wokuguqula ithumba. I-Tumor Mutation Burden (TMB) isetyenziswe njengenye isalathisi se-tumor immunogenicity. Ngokweziphumo zolingo lweklinikhi ze-KEYNOTE-158, phakathi kweendidi ezili-10 zamathumba aqinileyo aphezulu anyangwe nge-pembrolizumab, izigulane ezinotshintsho lwe-10 ubuncinane nge-megabase nganye (i-TMB ephezulu) zinezinga eliphezulu lokuphendula kunezo zine-TMB ephantsi. Kuyafaneleka ukuqaphela ukuba kolu phononongo, i-TMB yayiyi-predictor ye-PFS, kodwa ayizange ikwazi ukuqikelela i-OS.

Impendulo yonyango lwe-immune iqhutywa ikakhulu kukuqatshelwa kweeseli ze-T zama-antigens amatsha. I-immunogenicity enxulumene ne-TMB ephezulu ikwaxhomekeke kwizinto ezahlukeneyo, kubandakanywa ne-tumor neoantigen enikezelwe lithumba; Isixokelelwano sokhuselo lomzimba siyayibona i-tumor neoantigens; Ikhono lomninimzi ukuqalisa iimpendulo ze-antigen-specific. Umzekelo, idatha icebisa ukuba amathumba anokungena okuphezulu kwezinye iiseli zokuzikhusela komzimba anokuba ne-inhibitory regulatory T cell (Treg) clone amplification. Ukongeza, uluhlu lwe-TMB lunokwahluka kumandla e-TMB neoantigens, njengoko indawo echanekileyo yokuguqulwa nayo idlala indima ebalulekileyo; Ukuguqulwa kweendlela ezahlukeneyo zokubonisa i-antigen kunokuchaphazela umboniso (okanye ukungabikho) kwee-antigens ezintsha kwi-immune system, ebonisa ukuba iimpawu ze-tumor intrinsic kunye ne-immunological kufuneka zihambelane ukwenzela ukuvelisa iimpendulo ze-ICI ezifanelekileyo.

Okwangoku, i-TMB ilinganiswa ngokulandelelana kwesizukulwana esilandelayo (NGS), esinokuhluka phakathi kwamaziko ahlukeneyo (ngaphakathi) okanye amaqonga orhwebo asetyenziswayo. I-NGS ibandakanya ulandelelwano lwe-exome epheleleyo (WES), ulandelelwano lwe-genome epheleleyo, kunye nolandelelwano olujoliswe kuyo, olunokufunyanwa kwizicubu zethumba kunye nokujikeleza i-tumor DNA (ctDNA). Kuyaphawuleka ukuba iintlobo ezahlukeneyo ze-tumor zinoluhlu olubanzi lwe-TMB, kunye ne-immunogenic tumors ezifana ne-melanoma, i-NSCLC, kunye ne-squamous cell carcinoma enamanqanaba aphezulu e-TMB. Ngokufanayo, iindlela zokubona ezilungiselelwe iintlobo ezahlukeneyo zethumba zineenkcazo ezahlukeneyo zexabiso le-TMB threshold. Kuphononongo lwe-NSCLC, i-melanoma, i-urothelial carcinoma, kunye nomhlaza omncinci we-cell lung, ezi ndlela zokufumanisa zisebenzisa iindlela ezahlukeneyo zokuhlalutya (ezifana ne-WES okanye i-PCR yokufumanisa amanani athile eejeni ezihambelanayo) kunye ne-thresholds (i-TMB ephezulu okanye i-TMB ephantsi).

I-Microsatellites azinzanga kakhulu. I-Microsatellite engazinzanga kakhulu (MSI-H), njenge-pan cancer biomarker ye-ICI impendulo, inomsebenzi ogqwesileyo wokuqikelela ukusebenza kwe-ICI kwiintlobo ezahlukeneyo zomhlaza. I-MSI-H iyisiphumo sokungahambi kakuhle kokulungiswa kweziphene (dMMR), okukhokelela kwisantya esiphezulu sokuguqulwa, ngokukodwa kwimimandla ye-microsatellite, okubangelwa ukuveliswa kwenani elikhulu lama-antigens amatsha kwaye ekugqibeleni kubangele impendulo ye-clonal immune. Ngenxa yomthwalo ophezulu wokuguquka obangelwa yi-dMMR, i-tumor ye-MSI-H inokuqwalaselwa njengoluhlobo lomthwalo ophezulu we-mutation (TMB) tumor. Ngokusekelwe kwiziphumo zolingo lweklinikhi ze-KEYNOTE-164 kunye ne-KEYNOTE-158, i-FDA ivume i-pembrolizumab kunyango lwe-MSI-H okanye i-dMMR tumors. Eli lelinye lamachiza okuqala omhlaza wepan avunywe yi-FDA eqhutywa yi-tumor biology kune-histology.

Ngaphandle kwempumelelo enkulu, kukwakho nemiba ekufuneka uyiqaphele xa usebenzisa imeko ye-MSI. Ngokomzekelo, ukuya kuthi ga kwi-50% yezigulane ze-dMMR zomhlaza we-colorectal azikho impendulo kunyango lwe-ICI, ebonisa ukubaluleka kwezinye iimpawu ekuchazeni impendulo. Ezinye iimpawu zangaphakathi zamathumba angenako ukuvavanywa ngamaqonga okubona angoku anokuba negalelo. Ngokomzekelo, kukho iingxelo zokuba izigulane ezinokuguqulwa kofuzo kwi-encoding subunits ebalulekileyo ye-catalytic ye-polymerase delta (POLD) okanye i-polymerase ε (POLE) kwingingqi ye-DNA ayinakho ukunyaniseka kokuphindaphinda kwaye ibonisa "i-super mutation" phenotype kumathumba abo. Ezinye zezi thumba ziye zandisa kakhulu ukungazinzi kwe-microsatellite (ngaloo ndlela ye-MSI-H), kodwa iiprotheyini zokulungisa ezingafaniyo azisweli (ngoko ke azikho i-dMMR).

Ukongezelela, ngokufana ne-TMB, i-MSI-H iphinda ichaphazeleke kwiindidi ze-antigen ezintsha eziveliswa ukungazinzi kwe-microsatellite, ukuqaphela umkhosi weentlobo ezintsha ze-antigen, kunye ne-host immune system yokuphendula. Nakwi-MSI-H uhlobo lwe-tumor, inani elikhulu leenguqu ze-nucleotide enye ziye zachongwa njengeenguqu zabagibeli (iinguqu ezingezona zomqhubi). Ngoko ke, ukuthembela kuphela kwinani le-microsatellites ezichongiweyo kwi-tumor akwanele; Olona hlobo lokwenene lwenguqu (echongiwe ngeeprofayili ezithile zokuguqula) lunokuphucula ukusebenza okuqikelelweyo koluphawu lwebhayoloji. Ukongeza, kuphela inani elincinci labaguli abanomhlaza abakwi-MSI-H tumors, ebonisa imfuno yangoku yee-biomarkers ezisebenza ngokubanzi. Ke ngoko, ukuchonga ezinye ii-biomarkers ezisebenzayo ukuqikelela ukusebenza kunye nokukhokela ulawulo lwezigulane kuhlala kuyindawo ebalulekileyo yophando.

Uphando lwebiomarker esekwe kumbutho

Ngenxa yokuba indlela yokusebenza ye-ICI kukubuyisela umva ukucinezelwa kweeseli zomzimba kunokuba ijolise ngokuthe ngqo kwiindlela zangaphakathi zeeseli zethumba, uphando olongezelelweyo kufuneka lugxininise ekuhlalutyweni ngokucokisekileyo imeko yokukhula kwethumba kunye nentsebenziswano phakathi kweeseli zethumba kunye neeseli zomzimba, ezinokunceda ukucacisa izinto ezichaphazela impendulo ye-ICI. Amaqela amaninzi ophando aye afunda ithumba okanye iimpawu zokhuselo lomzimba lweentlobo ezithile zeethishu, ezifana nethumba kunye neempawu zokuguqula ijini lomzimba, iintsilelo zokubonisa i-tumor antigen, okanye amaziko okhuselo lomzimba okanye i-aggregates (ezifana nezakhiwo ze-lymphoid ephezulu), ezinokuqikelela iimpendulo kwi-immunotherapy.

Abaphandi basebenzise i-NGS ukulandelelanisa ithumba kunye ne-immune exome kunye ne-transcriptome yezicubu zesigulana ngaphambi nasemva konyango lwe-ICI, kwaye baqhuba uhlalutyo lokucinga kwendawo. Ngokusebenzisa iimodeli ezininzi ezidibeneyo, ezidityaniswe nobuchule obunjengokulandelelaniswa kweseli enye kunye nemifanekiso yendawo, okanye iimodeli ze-omics ezininzi, ukukwazi ukuxela kwangaphambili iziphumo zonyango ze-ICI kuye kwaphuculwa. Ukongeza, indlela ebanzi yokuvavanya imiqondiso ye-tumor immune immune kunye neempawu zethumba elingaphakathi libonise amandla aqikelelweyo okuxela kwangaphambili. Umzekelo, indlela yolandelelwano yebhetshi ebanzi elinganisa ngaxeshanye ithumba kunye neempawu zokhuselo lomzimba ziphezulu kuneyantlukwano yohlalutyo olunye. Ezi ziphumo zibalaselisa imfuneko yokulinganisa ukusebenza kwe-ICI ngendlela ebanzi ngakumbi, kubandakanywa nokubandakanya iziphumo zovavanyo lwamandla omzimba omkhosi, iimpawu ze-tumor zangaphakathi, kunye namalungu omzimba we-tumor kwizigulana ezizimeleyo ukuze ziqikelele ngcono ukuba zeziphi izigulana eziya kusabela kunyango lwe-immunotherapy.

Ngenxa yobunzima bokubandakanya i-tumor kunye ne-host factor kuphando lwe-biomarker, kunye nesidingo esinokubakho sokudityaniswa kwexesha elide leempawu ze-immune microenvironment, abantu sele beqalisile ukuphonononga ii-biomarkers besebenzisa imodeli yekhompyuter kunye nokufunda koomatshini. Okwangoku, kuye kwavela ezinye izinto eziphunyeziweyo zophando kweli candelo, zibonisa ikamva le-oncology yobuqu encediswa kukufunda koomatshini.

Imingeni ejongene neempawu zebhayoloji ezisekwe kwithishu

Ukulinganiselwa kweendlela zokuhlalutya. Ezinye ii-biomarkers ezinentsingiselo ziqhuba kakuhle kwiintlobo ezithile zethumba, kodwa kungekhona kwezinye iintlobo zethumba. Nangona iimpawu ezithile zemfuza yethumba zinamandla okuxela kwangaphambili kune-TMB kunye nabanye, azinakusetyenziselwa ukuxilongwa kwawo onke amathumba. Kuphononongo olujolise kwizigulane ze-NSCLC, iimpawu zokuguqula i-gene zifunyenwe ziqikelele ngakumbi kwi-ICI esebenzayo kune-TMB ephezulu (≥ 10), kodwa ngaphezu kwesiqingatha sezigulane azikwazanga ukubona iimpawu zokuguqulwa kwemfuza.

I-Tumor heterogeneity. Indlela ye-biomarker ye-thishu esekelwe kwisampulu kuphela kwindawo enye yethumba, okuthetha ukuba ukuvavanywa kweendawo ezithile ze-tumor kusenokungabonakali ngokuchanekileyo ukubonakaliswa kwazo zonke ithumba kwisigulane. Umzekelo, uphononongo lufumene i-heterogeneity kwi-PD-L1 yokubonisa phakathi nangaphakathi kwamathumba, kwaye imiba efanayo ikhona kunye nezinye iimpawu zethishu.

Ngenxa yokuntsonkotha kweenkqubo zebhayoloji, uninzi lweempawu zebhayoloji ebezisetyenziswa ngaphambili zisenokuba zenziwe lula kakhulu. Ukongeza, iiseli ezikwi-tumor microenvironment (TME) zihlala zihamba, ke unxibelelwano oluboniswe kuhlalutyo lwendawo lusenokungameli intsebenziswano yokwenyani phakathi kweeseli zethumba kunye neeseli zomzimba. Nokuba i-biomarkers inokumela ngokufanelekileyo indawo yonke ye-tumor ngexesha elithile, ezi thagethi zisenokwenziwa kwaye zitshintshe ngokuguquguqukayo ekuhambeni kwexesha, nto leyo ebonisa ukuba umfanekiso okhawulezayo ngexesha elithile unokungameli utshintsho oluguquguqukayo kakuhle.

I-heterogeneity yesigulane. Nokuba utshintsho lwemfuzo olwaziwayo olunxulumene nokuxhathisa kwe-ICI luchongiwe, ezinye izigulana eziphethe i-biomarkers ezaziwayo zokuxhathisa zisenokuzuza, mhlawumbi ngenxa yemolekyuli kunye/okanye i-immune heterogeneity ngaphakathi kwethumba nakwiindawo ezahlukeneyo zethumba. Ngokomzekelo, ukusilela kwe-β 2-microglobulin (B2M) kunokubonisa ukuxhathisa kwamachiza okutsha okanye okufunyenweyo, kodwa ngenxa yokungafani kwe-B2M yokusilela phakathi kwabantu kunye nangaphakathi kwamathumba, kunye nokusebenzisana kweendlela zokutshintshwa kwe-immune recognition ezi zi gulane, ukunqongophala kwe-B2M akunako ukuqikelela ngokucacileyo ukunganyangeki kweyeza lomntu ngamnye. Ke ngoko, nangona kukho ukusilela kwe-B2M, izigulana zisenokuzuza kunyango lwe-ICI.

Iimpawu zebhayoloji ezisekwe kumbutho
Ukubonakaliswa kwee-biomarkers kunokutshintsha ngokuhamba kwexesha kunye nefuthe lonyango. Uvavanyo lwe-Static kunye nolunye lwe-tumor kunye ne-immunobiology lunokungahoywa olu tshintsho, kwaye utshintsho kwi-tumor TME kunye ne-host immune response amanqanaba anokungahoywa. Izifundo ezininzi zibonise ukuba ukufumana iisampulu ngaphambi nangexesha lonyango kunokuchonga ngokuchanekileyo utshintsho olunxulumene nonyango lwe-ICI. Oku kuqaqambisa ukubaluleka kovavanyo oluguqukayo lwe-biomarker.

Iimpawu ezisekelwe kwigazi
Inzuzo yohlalutyo lwegazi ilele kwisakhono salo sokuvavanya ngokwebhayoloji zonke izilonda zethumba lomntu ngamnye, ebonisa ufundo oluyi-avareji kunokufundwa kwendawo ethile, iyenza ifaneleke ngokukodwa ukuvavanya utshintsho oluguquguqukayo olunxulumene nonyango. Iziphumo zophando ezininzi zibonise ukuba ukusebenzisa i-tumor DNA (ctDNA) okanye iiseli zethumba ezijikelezayo (CTC) ukuvavanya isifo esishiyekileyo esincinci (MRD) sinokukhokela izigqibo zonyango, kodwa ezi mvavanyo zinolwazi olulinganiselweyo malunga nokuqikelela ukuba izigulane zinokuzuza kwii-immunotherapies ezifana ne-ICI. Ke ngoko, uvavanyo lwe-ctDNA kufuneka ludityaniswe nezinye iindlela zokulinganisa ukusebenza kwamajoni omzimba okanye ukubamba amandla omzimba. Kule nkalo, inkqubela yenziwe kwi-immunophenotyping ye-peripheral blood mononuclear cells (PBMCs) kunye nohlalutyo lweproteomic ye-extracellular vesicles kunye ne-plasma. Ngokomzekelo, i-peripheral immune cell subtypes (ezifana neeseli ze-CD8 + T), ukubonakaliswa okuphezulu kwee-molecule ze-immune checkpoint (ezifana ne-PD1 kwiiseli ze-CD8 + T ze-peripheral), kunye namanqanaba aphakamileyo eeprotheni ezahlukeneyo kwi-plasma (njenge-CXCL8, i-CXCL10, i-IL-6, i-IL-10, i-PRAP1, kunye ne-VEGDNA esebenzayo yokuncedisa i-biodynamics kwi-biodynamics). Inzuzo yezi ndlela zintsha kukuba banokuhlola utshintsho ngaphakathi kwethumba (elifana notshintsho oluchongwe yi-ctDNA) kwaye banokutyhila utshintsho kumajoni omzimba wesigulana.

IiRadiomics
Izinto eziqikelelwayo zedatha yemifanekiso zinokoyisa ngokufanelekileyo imida yesampulu ye-biomarker yezicubu kunye ne-biopsy, kwaye inokubona lonke ithumba kunye nezinye iisayithi zemetastatic nangaliphi na ixesha. Ke ngoko, banokuba yinxalenye ebalulekileyo yee-non-invasive biomarkers kwixesha elizayo. I-Delta radiomics ingabala ngokobungakanani utshintsho kwiimpawu ezininzi ze-tumor (ezifana nobukhulu be-tumor) ngamaxesha ahlukeneyo, njengangaphambili nasemva konyango lwe-ICI, ngexesha lonyango, kunye nokulandelwa okulandelayo. I-Delta radiomics ayinakuqikelela kuphela impendulo yokuqala okanye ingabikho kunyango lwakwangoko, kodwa kwakhona ichonge ukuchasana okufunyenweyo kwi-ICI ngexesha langempela kwaye ibeke iliso nakuphi na ukuphindaphinda emva kokuxolelwa okupheleleyo. Imodeli yokucinga ephuhliswe ngeteknoloji yokufunda ngomatshini ibhetele ngakumbi kunomgangatho we-RECIST wendabuko ekuqikeleleni impendulo yonyango kunye neziganeko ezimbi ezinokwenzeka. Uphando lwangoku lubonisa ukuba ezi modeli zeradiomics zinendawo ephantsi kwegophe (AUC) ukuya kuthi ga kwi-0.8 ukuya kwi-0.92 ekuqikeleleni impendulo yonyango lomzimba.

Enye inzuzo yeeradiomics kukukwazi kwayo ukuchonga ngokuchanekileyo ukuqhubela phambili kwepseudo. Imodeli ye-radiomics eyakhiwe ngokufunda komatshini inokwahlula ngokufanelekileyo phakathi kokuqhubela phambili okwenyaniso kunye nobuxoki ngokulinganisa kwakhona idatha ye-CT okanye ye-PET ye-tumor nganye, kubandakanywa izinto ezifana nokuma, ukuqina, kunye nokuthungwa, kunye ne-AUC ye-0.79. Le mifuziselo ye-radiomics ingasetyenziselwa kwixesha elizayo ukuphepha ukupheliswa kwangaphambi kwexesha lonyango ngenxa yokungaqondi kakuhle ukuqhubela phambili kwesifo.

I-microbiota yamathumbu
I-biomarkers ye-gut microbiota kulindeleke ukuba iqikelele impendulo yonyango ye-ICI. Izifundo ezininzi zibonise ukuba i-gut microbiota ethile inxulumene ngokusondeleyo nempendulo yeentlobo ezahlukeneyo zomhlaza kunyango lwe-ICI. Ngokomzekelo, kwizigulane ezine-melanoma kunye nomhlaza wesibindi, ubuninzi bebhaktheriya ye-Ruminococcaceae ihambelana ne-PD-1 immunotherapy impendulo. Ukutyetyiswa kwe-Akkermansia muciniphila kuxhaphakile kwizigulane ezinomhlaza wesibindi, umhlaza wemiphunga, okanye i-renal cell carcinoma, ephendula kakuhle kunyango lwe-ICI.

Ukongeza, imodeli entsha yokufunda koomatshini inokuzimela kwiintlobo zethumba kwaye inxulumanise ijenari ethile yebhaktheriya yamathumbu kunye nempendulo yonyango lwe-immunotherapy. Olunye uphononongo lukwaveze indima ethile edlalwa ngamaqela ebhaktiriya ekulawuleni amajoni omzimba, ephonononga ngakumbi indlela yokuthintela okanye yokukhuthaza ukuphuma komzimba kwiiseli zomhlaza.

Unyango lweNeoadjuvant
Uvavanyo olunamandla lwebhayoloji yethumba lunokukhokela izicwangciso zonyango lwezonyango ezilandelayo. Ulingo lonyango lwe-neoadjuvant lunokuvavanya isiphumo sonyango ngoxolelo lwe-pathological kwimizekelo yotyando. Kunyango lwe-melanoma, impendulo yokuqala ye-pathological (MPR) inxulunyaniswa nokuphindaphinda izinga lokusinda simahla. Kwilingo le-PRADO, abaphandi banquma amanyathelo okungenelela kwekliniki elandelayo, njengotyando kunye / okanye unyango lwe-adjuvant, olusekelwe kwisigulane esithile sedatha yokuxolelwa kwe-pathological.

Phakathi kweentlobo ezahlukeneyo zomhlaza, ukhetho olutsha lonyango lwe-adjuvant lusenalo uthelekiso lwentloko. Ke ngoko, ukhetho phakathi kwe-immunotherapy monotherapy okanye unyango oludibeneyo luhlala lugqitywa ngokudibeneyo ngugqirha okhoyo kunye nesigulana. Okwangoku, abaphandi baye bavelisa i-interferon gamma (i-IFN gamma) equlethe i-gene ye-10 njenge-biomarker yokuqikelela ukuxolelwa kwe-pathological kwi-melanoma emva konyango lwe-neoadjuvant. Baye badibanisa ngakumbi ezi mpawu kwi-algorithm yokukhetha izigulane ezineempendulo ezinamandla okanye ezibuthathaka kunyango lwe-neoadjuvant. Kuphononongo olulandelwayo olubizwa ngokuba yi-DONIMI, abaphandi basebenzise eli nqaku, lidibaniswe nohlalutyo olunzima ngakumbi, kungekhona nje ukuqikelela impendulo yonyango, kodwa kunye nokufumanisa ukuba yeyiphi inqanaba le-III izigulane ze-melanoma ezifuna ukongezwa kwe-histone deacetylase inhibitors (HDACi) ukunyusa impendulo kwi-neoadjuvant ICI unyango.

Imodeli ye-tumor evela kwizigulane
Iimodeli ze-in vitro tumor zinamandla okuqikelela iimpendulo ezithile zesigulana. Ngokungafaniyo neqonga le-in vitro elisetyenziselwa uhlalutyo lokuphendula kweziyobisi lwe-hematological malignancies, amathumba aqinileyo ajongene nemiceli mngeni emikhulu ngenxa ye-tumor microstructure yawo ekhethekileyo kunye nokunxibelelana kwe-immune immune. Inkcubeko yeseli yethumba elula ayinakuphinda ngokulula ezi mpawu zintsonkothileyo. Kule meko, ithumba elifana namalungu okanye iitshiphu zelungu ezisuka kwizigulana zinokubuyekeza le mida yesakhiwo, njengoko zinokugcina ubume beseli yethumba yoqobo kwaye zilinganise ukusebenzisana ne-lymphoid kunye neeseli zokhuselo lomzimba ze-myeloid ukuvavanya iimpendulo ze-ICI ngendlela ethile yesigulana, ngaloo ndlela ivelisa kwakhona ngokuchanekileyo ngakumbi iimpawu zebhayoloji kwindawo enenyani enomacala amathathu.

Izifundo ezininzi eziyimpumelelo e-China nase-United States zamkele le modeli intsha yokuthembeka inamacala amathathu e-vitro tumor. Iziphumo zibonisa ukuba ezi modeli zinokuqikelela ngokufanelekileyo impendulo yomhlaza wemiphunga, umhlaza wekolon, umhlaza wamabele, imelanoma kunye namanye amathumba kwi-ICI. Oku kubeka isiseko sokuqinisekisa ngakumbi kunye nokulungelelanisa ukusebenza okuqikelelweyo kwezi modeli.