litaba

Immunotherapy e tlisitse liphetoho tsa phetoho kalafong ea lihlahala tse kotsi, empa ho ntse ho na le bakuli ba bang ba ke keng ba rua molemo. Ka hona, li-biomarker tse nepahetseng li hlokahala ka potlako lits'ebetsong tsa bongaka ho bolela esale pele katleho ea immunotherapy, e le ho eketsa katleho le ho qoba chefo e sa hlokahaleng.

FDA e amohetse li-biomarker

Tlhaloso ea PD-L1. Tekolo ea maemo a polelo ea PD-L1 ka immunohistochemistry (IHC) e fana ka lintlha tsa tumor proportion score (TPS), e leng peresente ea lisele tse nang le lera le nang le lera le nang le matla leha e le afe liseleng tsa hlahala tse ntseng li phela. Litekong tsa bongaka, tlhahlobo ena e sebetsa e le tlhahlobo e thusang ea tlhahlobo ea kalafo ea mofetše o seng o monyane oa lisele tsa matšoafo (NSCLC) ka pembrolizumab. Haeba TPS ea sampuli e le ≥ 1%, polelo ea PD-L1 e nkoa; TPS ≥ 50% e bonts'a polelo e phahameng ea PD-L1. Tekong ea pele ea Phase 1 (KEYNOTE-001), tekanyo ea karabelo ea bakuli ho PD-L1 TPS> 50% sehlotšoana se sebelisang pembrolizumab e ne e le 45.2%, ha ho sa tsotellehe TPS, tekanyo ea karabo ea bakuli bohle ba fumanang phekolo ena ea immune checkpoint inhibitor (ICI) e ne e le 19.4%. Teko e latelang ea 2/3 (KEYNOTE-024) e fane ka bakuli ba PD-L1 TPS> 50% ho fumana pembrolizumab le chemotherapy e tloaelehileng, 'me liphello li bontšitse ntlafatso e kholo ea ho phela ka kakaretso (OS) ho bakuli ba fumanang phekolo ea pembrolizumab.

Leha ho le joalo, ts'ebeliso ea PD-L1 ho bolela esale pele likarabo tsa ICI e lekantsoe ke lintlha tse fapaneng. Taba ea pele, monyetla o nepahetseng bakeng sa mefuta e fapaneng ea mofetše oa fapana. Mohlala, Pabolizumab e ka sebelisoa ha polelo ea tumor PD-L1 ea bakuli ba nang le mofetše oa mala, mofets'e oa esophageal, mofets'e oa senya le mofets'e oa matšoafo ke 1%, 10% le 50% ka ho latellana. Taba ea bobeli, ho lekola palo ea lisele tsa polelo ea PD-L1 ho fapana ho latela mofuta oa mofets'e. Ka mohlala, phekolo ea squamous cell carcinoma e tloaelehileng kapa ea metastatic ea hlooho le molala e ka khetha ho sebelisa mokhoa o mong oa tlhahlobo o amohelehang oa FDA, Comprehensive Positive Score (CPS). Taba ea boraro, ha ho na khokahano lipakeng tsa polelo ea PD-L1 mefuteng e fapaneng ea mofets'e le karabelo ea ICI, e bonts'ang hore mokokotlo oa hlahala e ka ba ntlha ea bohlokoa ho boleleng li-biomarker tsa ICI. Ka mohlala, ho ea ka liphetho tsa tlhahlobo ea CheckMate-067, boleng bo fosahetseng ba PD-L1 ka melanoma ke 45% feela. Qetellong, liphuputso tse ngata li fumane hore polelo ea PD-L1 ha e lumellane ho pholletsa le maqeba a fapaneng a hlahala ho mokuli a le mong, esita le ka har'a hlahala e tšoanang. Ka kakaretso, leha liteko tsa pele tsa tleliniki tsa NSCLC li khothalelitse lipatlisiso mabapi le polelo ea PD-L1 e le sesupo sa biomarker e ka bang teng, ts'ebeliso ea eona ea bongaka mefuteng e fapaneng ea mofetše e ntse e sa hlaka.

Moroalo oa phetoho ea hlahala. Tlhōrō ea Phetoho ea Lihlahala (TMB) e 'nile ea sebelisoa e le sesupo se seng sa tumor immunogenicity. Ho ea ka liphetho tsa liteko tsa kliniki tsa KEYNOTE-158, har'a mefuta e 10 ea lihlahala tse tiileng tse tsoetseng pele tse tšoaroang ka pembrolizumab, bakuli ba nang le bonyane liphetoho tse 10 ka megabase (e phahameng TMB) ba ne ba e-na le tekanyo e phahameng ea ho arabela ho feta ba nang le TMB e tlaase. Ho bohlokoa ho hlokomela hore thutong ena, TMB e ne e le selelekela sa PFS, empa ha ea khona ho bolela OS esale pele.

Karabelo ea kalafo ea 'mele ea ho itšireletsa mafung e tsamaisoa haholo-holo ke ho lemoha lisele tsa T tsa li-antigen tse ncha. The immunogenicity amanang le TMB e phahameng e boetse e itšetlehile ka lintlha tse sa tšoaneng, ho kenyelletsa le hlahala neoantigen e hlahisoang ke hlahala; Tsamaiso ea 'mele ea ho itšireletsa mafung e lemoha li-neoantigens tsa hlahala; Bokhoni ba moamoheli ho qala likarabo tse ikhethileng tsa antigen. Mohlala, data e fana ka maikutlo a hore lihlahala tse kenang ka ho fetesisa liseleng tse ling tsa 'mele tsa ho itšireletsa mafung li kanna tsa ba le matlafatso ea li-clone tsa T cell (Treg). Ho feta moo, mefuta ea TMB e ka fapana le bokhoni ba li-neoantigens tsa TMB, kaha sebaka se nepahetseng sa phetoho le sona se phetha karolo ea bohlokoa; Liphetoho tse tsamaisanang le litsela tse fapaneng tsa tlhahiso ea antigen li ka ama tlhahiso (kapa ho se hlahise) ha li-antigen tse ncha tsamaisong ea 'mele ea ho itšireletsa mafung, e leng se bontšang hore litšobotsi tsa tumor intrinsic le immunological li tlameha ho lumellana e le hore li hlahise likarabo tse nepahetseng tsa ICI.

Hajoale, TMB e lekantsoe ka tatellano ea moloko o latelang (NGS), e ka 'nang ea fapana ho ea ka litsi tse fapaneng (ka hare) kapa sethala sa khoebo se sebelisoang. NGS e kenyelletsa tatellano e felletseng ea exome (WES), tatellano ea liphatsa tsa lefutso, le tatellano e lebisitsoeng, e ka fumanoang ho tsoa ho lisele tsa tumor le ho potoloha tumor DNA (ctDNA). Ke habohlokoa ho hlokomela hore mefuta e fapaneng ea lihlahala e na le mefuta e mengata ea TMB, e nang le lihlahala tsa immunogenic tse kang melanoma, NSCLC, le squamous cell carcinoma tse nang le maemo a phahameng ka ho fetisisa a TMB. Ka mokhoa o ts'oanang, mekhoa ea ho lemoha e etselitsoeng mefuta e fapaneng ea hlahala e na le litlhaloso tse fapaneng tsa litekanyetso tsa TMB threshold. Thutong ea NSCLC, melanoma, urothelial carcinoma, le mofetše o monyenyane oa lisele tsa matšoafo, mekhoa ena ea ho lemoha e sebelisa mekhoa e fapaneng ea ho hlahloba (e kang WES kapa PCR ho lemoha lipalo tse itseng tsa liphatsa tsa lefutso tse amanang) le menyako (TMB e phahameng kapa TMB tlase).

Li-microsatellites ha lia tsitsa haholo. Microsatellite e sa tsitsang haholo (MSI-H), joalo ka biomarker ea kankere ea pan bakeng sa karabelo ea ICI, e na le ts'ebetso e ntle haholo ea ho bolela esale pele katleho ea ICI mefuteng e fapaneng ea mofetše. MSI-H e bakoa ke mefokolo ea ho lokisoa ka tsela e sa lumellaneng (dMMR), e lebisang ho sekhahla se phahameng sa phetoho, haholo-holo libakeng tsa microsatellite, e leng se hlahisang tlhahiso ea palo e kholo ea li-antigen tse ncha 'me qetellong e baka karabelo ea 'mele ea ho itšireletsa mafung ea clonal. Ka lebaka la moroalo o phahameng oa phetoho o bakoang ke dMMR, lihlahala tsa MSI-H li ka nkoa e le mofuta oa moroalo o phahameng oa phetoho (TMB) tumor. Ho ipapisitsoe le liphetho tsa liteko tsa bongaka tsa KEYNOTE-164 le KEYNOTE-158, FDA e amohetse pembrolizumab bakeng sa kalafo ea lihlahala tsa MSI-H kapa dMMR. Ena ke e 'ngoe ea litlhare tsa pele tsa mofetše oa pan tse amohetsoeng ke FDA e tsamaisoang ke tumor biology ho fapana le histology.

Leha ho na le katleho e kholo, ho boetse ho na le litaba tseo u lokelang ho li ela hloko ha u sebelisa boemo ba MSI. Ka mohlala, ho fihlela ho 50% ea bakuli ba kankere ea mala ea dMMR ha ba na karabo ho phekolo ea ICI, e totobatsang bohlokoa ba likarolo tse ling ho bolela esale pele karabelo. Likarolo tse ling tsa kahare tsa lihlahala tse ke keng tsa hlahlojoa ke li-platform tsa hona joale tsa ho lemoha e kanna ea ba lintlha tse tlatsetsang. Ka mohlala, ho bile le litlaleho tsa hore bakuli ba nang le liphetoho tsa liphatsa tsa lefutso tse kenyang li-catalytic subunits tsa polymerase delta (POLD) kapa polymerase ε (POLE) sebakeng sa DNA ha ba na botšepehi ba ho ikatisa 'me ba bontša "super mutation" phenotype lihlahala tsa bona. Tse ling tsa lihlahala tsena li ekelitse ho se tsitse ha microsatellite (ka hona e le tsa MSI-H), empa liprotheine tsa ho lokisa tse sa lumellaneng ha li haelle (ka hona ha li dMMR).

Ho phaella moo, ho tšoana le TMB, MSI-H e boetse e angoa ke mefuta e mecha ea li-antigen e hlahisoang ke ho se tsitse ha microsatellite, ho amoheloa ha batho ba mefuta e mecha ea li-antigen, le ho arabela tsamaiso ea 'mele ea ho itšireletsa mafung. Esita le lihlahala tsa mofuta oa MSI-H, palo e kholo ea liphetoho tsa nucleotide e le 'ngoe e fumanoe e le liphetoho tsa baeti (liphetoho tse seng tsa mokhanni). Ka hona, ho itšetleha feela ka palo ea li-microsatellites tse khethiloeng ka har'a hlahala ha hoa lekana; Mofuta oa 'nete oa phetoho (e bonts'itsoeng ka li-profiles tse itseng tsa phetoho) e ka ntlafatsa ts'ebetso e boletsoeng esale pele ea biomarker ena. Ntle le moo, ke karolo e nyane feela ea bakuli ba mofets'e bao e leng ba lihlahala tsa MSI-H, ho bonts'a tlhoko ea hajoale ea li-biomarker tse sebelisoang haholo. Ka hona, ho tsebahatsa li-biomarker tse ling tse sebetsang ho bolela esale pele katleho le ho tataisa tsamaiso ea bakuli e ntse e le sebaka sa bohlokoa sa lipatlisiso.

Patlisiso ea biomarker e thehiloeng ho mokhatlo

Ka lebaka la hore ts'ebetso ea ICI ke ho khutlisa khatello ea lisele tsa 'mele ho fapana le ho lebisa ka kotloloho litselaneng tsa lisele tsa tumor, lipatlisiso tse ling li lokela ho tsepamisa maikutlo ho hlahlobisiseng tikoloho ea kholo ea hlahala le tšebelisano lipakeng tsa lisele tsa tumor le lisele tsa' mele tsa 'mele, tse ka thusang ho hlakisa lintlha tse amang karabelo ea ICI. Lihlopha tse ngata tsa lipatlisiso li ithutile ka hlahala kapa likarolo tsa 'mele tsa ho itšireletsa mafung tsa mefuta e itseng ea lisele, joalo ka tumor le liphatsa tsa lefutso tsa 'mele, likhaello tsa tlhahiso ea tumor antigen, kapa litsi tsa 'mele oa ho itšireletsa mafung kapa li-aggregates (joalo ka meaho e phahameng ea lymphoid), e ka bolelang esale pele likarabo tsa immunotherapy.

Bafuputsi ba sebelisitse NGS ho tatellana le hlahala le ts'oaetso ea 'mele ea ho itšireletsa mafung le transcriptome ea lisele tsa mokuli pele le kamora kalafo ea ICI, mme ba etsa tlhahlobo ea litšoantšo tsa sebaka. Ka ho sebelisa mefuta e mengata e kopantsoeng, e kopantsoeng le mekhoa e kang tatellano ea sele e le 'ngoe le litšoantšo tsa sebaka, kapa mefuta e mengata ea li-omics, bokhoni ba ho bolela esale pele ba liphello tsa phekolo ea ICI bo ntlafalitsoe. Ntle le moo, mokhoa o pharalletseng oa ho lekola matšoao a 'mele oa ho itšireletsa mafung le litšoaneleho tsa tumor tsa kahare le ona o bonts'itse bokhoni bo matla ba ho bolela esale pele. Ka mohlala, mokhoa o pharaletseng oa tatellano ea li-batch oo ka nako e le 'ngoe o lekanyetsang hlahala le litšobotsi tsa' mele oa ho itšireletsa mafung o phahametse phetoho e le 'ngoe ea tlhahlobo. Liphetho tsena li totobatsa tlhokahalo ea ho etsisa katleho ea ICI ka mokhoa o pharaletseng haholoanyane, ho kenyelletsa le ho kenyelletsa liphetho tsa tlhahlobo ea matla a 'mele oa ho itšireletsa mafung, litšoaneleho tsa tumor tsa kahare, le likarolo tsa 'mele oa ho itšireletsa mafung ho bakuli ka bomong ho bolela esale pele hore na bakuli ba tla arabela joang ho immunotherapy.

Ka lebaka la ho rarahana ha ho kenyelletsa hlahala le lintlha tse amohelang lipatlisiso tsa biomarker, hammoho le tlhoko e ka bang teng ea ho kopanngoa ha longitudinal ea likarolo tsa immune microenvironment, batho ba se ba qalile ho hlahloba li-biomarker ba sebelisa mohlala oa khomphutha le ho ithuta ka mochini. Hajoale, ho hlahile likatleho tse ling tsa bohlokoa lefapheng lena, tse bonts'ang bokamoso ba oncology ea motho ka mong e thusoang ke ho ithuta ka mochini.

Mathata a tobaneng le li-biomarker tse thehiloeng ho lisele

Meeli ea mekhoa ea ho hlahloba. Li-biomarker tse ling tse nang le moelelo li sebetsa hantle mefuteng e itseng ea hlahala, empa eseng hakaalo mefuteng e meng ea hlahala. Le hoja likarolo tsa lefutso tse khethehileng tsa tumor li na le bokhoni bo matla ba ho bolela esale pele ho feta TMB le tse ling, li ke ke tsa sebelisoa bakeng sa tlhahlobo ea lihlahala tsohle. Phuputsong e lebisitseng ho bakuli ba NSCLC, likarolo tsa phetoho ea liphatsa tsa lefutso li ile tsa fumanoa li bolela esale pele ka katleho ea ICI ho feta TMB e phahameng (≥ 10), empa bakuli ba fetang halofo ba ne ba sitoa ho lemoha likarolo tsa phetoho ea liphatsa tsa lefutso.

Heterogeneity ea hlahala. Mokhoa oa biomarker o thehiloeng ho lisele o nka feela lisampole sebakeng se le seng sa hlahala, ho bolelang hore tlhahlobo ea likarolo tse itseng tsa hlahala e kanna ea se ke ea bonahatsa ka nepo polelo e akaretsang ea lihlahala tsohle ho mokuli. Mohlala, liphuputso li fumane heterogeneity polelong ea PD-L1 lipakeng le ka hare ho lihlahala, 'me litaba tse ts'oanang li teng ka matšoao a mang a lisele.

Ka lebaka la ho rarahana ha litsamaiso tsa baeloji, li-biomarker tse ngata tse neng li kile tsa sebelisoa e kanna eaba li nolofalitsoe ho feta tekano. Ho feta moo, lisele tse ka har'a tumor microenvironment (TME) hangata lia tsamaea, kahoo litšebelisano tse bonts'itsoeng tlhahlobong ea sebaka li kanna tsa se ke tsa emela litšebelisano tsa 'nete lipakeng tsa lisele tsa hlahala le lisele tsa 'mele. Leha li-biomarker li ka emela tikoloho eohle ea hlahala ka nako e itseng, lipehelo tsena li ntse li ka susumetsoa le ho fetoha ka matla ha nako e ntse e ea, ho bonts'a hore setšoantšo se le seng ka nako se kanna sa se ke sa emela liphetoho tse matla hantle.

Mokuli o fapaneng. Esita le haeba liphetoho tse tsejoang tsa liphatsa tsa lefutso tse amanang le khanyetso ea ICI li fumanoa, bakuli ba bang ba jereng li-biomarker tse tsejoang tsa ho hanyetsa ba ntse ba ka rua molemo, mohlomong ka lebaka la limolek'hule le / kapa ho itšireletsa mafung ka har'a hlahala le libakeng tse fapaneng tsa hlahala. Ka mohlala, khaello ea β 2-microglobulin (B2M) e ka 'na ea bontša khanyetso e ncha kapa e fumanoeng ea lithethefatsi, empa ka lebaka la ho fapana ha khaello ea B2M pakeng tsa batho ka bomong le ka har'a lihlahala, hammoho le ho sebelisana ha mekhoa ea ho amohela tšireletso ea' mele ho bakuli bana, ho haella ha B2M ho ka 'na ha se ke ha bolela esale pele ka matla ho hanyetsa lithethefatsi ka bomong. Ka hona, leha ho na le khaello ea B2M, bakuli ba ntse ba ka rua molemo kalafong ea ICI.

Li-biomarker tsa longitudinal tse thehiloeng ho mokhatlo
Polelo ea li-biomarker e ka fetoha ha nako e ntse e ea le ka phello ea kalafo. Litlhahlobo tse tsitsitseng le tse le 'ngoe tsa lihlahala le immunobiology li ka hlokomoloha liphetoho tsena,' me liphetoho tsa TME ea tumor le maemo a karabelo ea 'mele oa ho itšireletsa mafung le tsona li ka hlokomolohuoa. Liphuputso tse ngata li bontšitse hore ho fumana mehlala pele le nakong ea phekolo ho ka tseba hantle liphetoho tse amanang le phekolo ea ICI. Sena se totobatsa bohlokoa ba tlhahlobo e matla ea biomarker.

Li-biomarker tse thehiloeng maling
Molemo oa ho hlahloba mali o itšetlehile ka bokhoni ba eona ba ho hlahloba ka mokhoa oa likokoana-hloko maqeba 'ohle a hlahala ka bomong, ho bonahatsa palo e tloaelehileng ea ho bala ho e-na le ho bala libaka tse itseng, ho etsa hore e tšoanelehe ka ho khetheha bakeng sa ho hlahloba liphetoho tse matla tse amanang le phekolo. Liphetho tse ngata tsa lipatlisiso li bonts'itse hore ho sebelisa tumor DNA (ctDNA) kapa circulating tumor cell (CTC) ho lekola lefu le fokolang la masala (MRD) ho ka tataisa liqeto tsa kalafo, empa liteko tsena li na le tlhaiso-leseling e fokolang mabapi le ho bolela esale pele hore na bakuli ba ka rua molemo ho immunotherapies joalo ka ICI. Ka hona, tlhahlobo ea ctDNA e hloka ho kopanngoa le mekhoa e meng ho lekanya ts'ebetso ea 'mele ea ho itšireletsa mafung kapa matla a ho itšireletsa mafung. Tabeng ena, ho entsoe tsoelo-pele ho immunophenotyping ea peripheral blood mononuclear cells (PBMCs) le tlhahlobo ea proteomic ea li-extracellular vesicles le plasma. Ka mohlala, peripheral immune cell subtypes (tse kang CD8 + T lisele), polelo e phahameng ea limolek'hule tsa ho hlahloba 'mele (joaloka PD1 ka lisele tsa CD8 + T tsa peripheral), le maemo a phahameng a liprotheine tse fapa-fapaneng tsa plasma (tse kang CXCL8, CXCL10, IL-6, IL-10, PRAP1, le VEGDNA e sebetsang e ka sebetsa e le lisebelisoa tsa VEGDdynamic). Molemo oa mekhoa ena e mecha ke hore e ka hlahloba liphetoho tse teng ka har'a hlahala (e tšoanang le liphetoho tse bonoang ke ctDNA) 'me e ka boela ea senola liphetoho tsamaisong ea 'mele ea ho itšireletsa mafung ea mokuli.

Li-radiomics
Lintlha tse boletsoeng esale pele tsa data ea setšoantšo li ka hlola mefokolo ea sampole ea biomarker ea lisele le biopsy, 'me li ka bona hlahala eohle le libaka tse ling tsa metastatic ka nako efe kapa efe. Ka hona, li ka fetoha karolo ea bohlokoa ea li-biomarker tse matla tse sa hlaseleng nakong e tlang. Li-radiomics tsa Delta li ka bala ka bongata liphetoho tsa likarolo tse ngata tsa hlahala (joalo ka boholo ba hlahala) ka linako tse fapaneng, joalo ka pele le ka mor'a kalafo ea ICI, nakong ea kalafo, le tatellano e latelang. Delta radiomics e ke ke ea bolela esale pele karabelo ea pele kapa e se nang letho kalafong ea pele, empa hape e tsebahatsa khanyetso e fumanoeng ho ICI ka nako ea nnete le ho lekola ho khutla hape ka mor'a tšoarelo e felletseng. Mokhoa oa ho etsa litšoantšo o ntlafalitsoeng ka theknoloji ea ho ithuta ka mochini o betere ho feta tloaelo ea RECIST ea ho bolela esale pele karabelo ea kalafo le liketsahalo tse mpe tse ka bang teng. Patlisiso ea hajoale e bonts'a hore mefuta ena ea radiomics e na le sebaka se ka tlase ho curve (AUC) ho fihla ho 0.8 ho isa ho 0.92 ho bolela esale pele karabelo ea kalafo ea 'mele ea ho itšireletsa mafung.

Molemo o mong oa radiomics ke bokhoni ba eona ba ho tseba ka nepo tsoelo-pele ea pseudo. Moetso oa radiomics o entsoeng ka ho ithuta ka mochini o ka khetholla ka nepo lipakeng tsa tsoelo-pele ea 'nete le ea bohata ka ho lekanya hape data ea CT kapa PET bakeng sa hlahala e' ngoe le e 'ngoe, ho kenyeletsoa lintlha tse kang sebopeho, matla, le sebopeho, ka AUC ea 0.79. Mehlala ena ea li-radiomics e ka sebelisoa nakong e tlang ho qoba ho felisoa pele ho nako ea kalafo ka lebaka la ho se nahanele ha tsoelo-pele ea mafu.

Intestinal microbiota
Li-biomarker tsa gut microbiota li lebelletsoe ho bolela esale pele karabelo ea kalafo ea ICI. Liphuputso tse ngata li bontšitse hore gut microbiota e itseng e amana haufi-ufi le karabelo ea mefuta e fapaneng ea mofetše ho ICI kalafo. Ka mohlala, ho bakuli ba nang le kankere ea melanoma le sebete, bongata ba libaktheria tsa Ruminococcaceae bo amahanngoa le karabo ea PD-1 immunotherapy. Matlafatso ea Akkermansia muciniphila e tloaelehile ho bakuli ba nang le mofetše oa sebete, mofetše oa matšoafo, kapa renal cell carcinoma, ba arabelang hantle kalafong ea ICI.

Ntle le moo, mofuta o mocha oa ho ithuta oa mochini o ka ikemela ho mefuta ea tumor mme oa amahanya mofuta o ikhethileng oa baktheria ea mala le karabelo ea kalafo ea immunotherapy. Liphuputso tse ling li boetse li senotse karolo e ikhethileng eo lihlopha tsa baktheria li e bapalang ho laola sesole sa 'mele, ho tsoela pele ho hlahloba mokhoa oa ho thibela kapa ho khothaletsa ho baleha ha lisele tsa mofetše.

Phekolo ea Neoadjuvant
Tlhahlobo e matla ea biology ea tumor e ka tataisa maano a latelang a kalafo ea bongaka. Teko ea Neoadjuvant Therapy e ka lekola phello ea kalafo ka ho phofa ha pathological ho mehlala ea opereishene. Kalafong ea melanoma, karabelo ea mantlha ea pathological (MPR) e amahanngoa le sekhahla sa ho pholoha mahala. Tekong ea PRADO, bafuputsi ba fumana mehato e latelang ea ho kena lipakeng tsa kliniki, joalo ka opereishene le / kapa kalafo ea adjuvant, e ipapisitseng le data e ikhethileng ea mokuli.

Har'a mefuta e fapaneng ea mofets'e, mekhoa e mengata e mecha ea kalafo ea adjuvant e ntse e haelloa ke papiso ea hlooho le hlooho. Ka hona, khetho pakeng tsa immunotherapy monotherapy kapa phekolo ea motsoako hangata e khethoa ka kopanelo ke ngaka e eang teng le mokuli. Hona joale, bafuputsi ba thehile karolo ea interferon gamma (IFN gamma) e nang le liphatsa tsa lefutso tse 10 e le biomarker bakeng sa ho bolela esale pele phokolo ea lefu la melanoma ka mor'a phekolo ea neoadjuvant. Ba boetse ba kopanya likarolo tsena ho algorithm ho khetha bakuli ba nang le likarabo tse matla kapa tse fokolang ho phekolo ea neoadjuvant. Phuputsong e latelang e bitsoang DONIMI, bafuputsi ba ile ba sebelisa lintlha tsena, tse kopantsoeng le tlhahlobo e rarahaneng haholoanyane, eseng feela ho bolela esale pele karabelo ea phekolo, empa hape le ho fumana hore na bakuli ba melanoma ba sethaleng sa III ba hloka ho eketsoa ha histone deacetylase inhibitors (HDACi) ho matlafatsa karabo ho neoadjuvant ICI kalafo.

Mohlala oa hlahala o tsoang ho bakuli
Mefuta ea tumor ea in vitro e na le monyetla oa ho bolela esale pele likarabo tse khethehileng tsa mokuli. Ho fapana le sethala sa in vitro se sebelisetsoang tlhahlobo ea karabelo ea lithethefatsi ea malignancies ea mali, lihlahala tse tiileng li tobane le mathata a maholo ka lebaka la sebopeho sa tsona se ikhethileng sa tumor le tšebelisano ea 'mele ea ho itšireletsa mafung. Setso se bonolo sa lisele tsa tumor ha se khone ho etsa likarolo tsena tse rarahaneng habonolo. Tabeng ena, hlahala e kang litho kapa litho tsa 'mele tse tsoang ho bakuli li ka lefella mefokolo ena ea sebopeho, kaha li ka boloka sebopeho sa lisele tsa tumor' me li etsisa litšebelisano le lisele tsa 'mele tsa lymphoid le myeloid ho lekola likarabo tsa ICI ka mokhoa o khethehileng oa mokuli, ka tsela e nepahetseng haholoanyane ho hlahisa likarolo tsa likokoana-hloko sebakeng sa sebele sa mahlakore a mararo.

Lithuto tse 'maloa tsa katleho Chaena le United States li amohetse mofuta ona o mocha oa ho tšepahala o phahameng oa mahlakore a mararo a in vitro tumor. Liphetho li bonts'a hore mefuta ena e ka bolela esale pele ka karabelo ea mofetše oa matšoafo, mofetše oa mala, mofetše oa matsoele, melanoma le lihlahala tse ling ho ICI. Sena se rala motheo oa ho netefatsa le ho tiisa ts'ebetso e boletsoeng esale pele ea mefuta ena.