labarai

Immunotherapy ya kawo sauye-sauye na juyin juya hali don maganin ciwon ciwon daji, amma har yanzu akwai wasu marasa lafiya waɗanda ba za su iya amfana ba. Sabili da haka, ana buƙatar masu amfani da kwayoyin halitta masu dacewa da gaggawa a cikin aikace-aikacen asibiti don tsinkayar tasirin immunotherapy, don haɓaka inganci da kuma guje wa guba mara amfani.

FDA ta amince da alamun halittu

Bayanin PD-L1. Ƙimar matakan maganganun PD-L1 ta immunohistochemistry (IHC) yana haifar da ƙimar ƙimar ƙari (TPS), wanda shine kashi na ɓangaren ɓangaren ko gaba ɗaya membrane na ƙwayoyin ƙwayar cuta na kowane ƙarfi a cikin tsiran ƙwayoyin ƙari. A cikin gwaje-gwajen asibiti, wannan gwajin yana aiki azaman gwajin bincike na taimako don maganin ci-gaban ciwon huhu na huhu (NSCLC) tare da pembrolizumab. Idan TPS na samfurin shine ≥ 1%, ana la'akari da magana PD-L1; TPS ≥ 50% yana nuna babban magana na PD-L1. A cikin gwaji na farko na Phase 1 (KEYNOTE-001), yawan amsawar marasa lafiya a cikin PD-L1 TPS> 50% subgroup ta amfani da pembrolizumab shine 45.2%, yayin da ba tare da la'akari da TPS ba, yawan amsawar duk marasa lafiya da ke karɓar wannan maganin rigakafin rigakafi (ICI) shine 19.4%. Gwajin gwaji na 2 / 3 na gaba (KEYNOTE-024) da bazuwar da aka ba marasa lafiya tare da PD-L1 TPS> 50% don karɓar pembrolizumab da daidaitattun ƙwayoyin cuta, kuma sakamakon ya nuna babban ci gaba a cikin rayuwa gabaɗaya (OS) a cikin marasa lafiya da ke karɓar magani na pembrolizumab.

Koyaya, aikace-aikacen PD-L1 a cikin tsinkayar martanin ICI yana iyakance ta dalilai daban-daban. Da fari dai, madaidaicin ƙofa na nau'ikan ciwon daji daban-daban ya bambanta. Alal misali, Pabolizumab za a iya amfani da lokacin da ƙari PD-L1 magana na marasa lafiya da ciwon ciki ciwon daji, esophageal ciwon daji, mafitsara ciwon daji da kuma huhu ciwon daji ne 1%, 10% da kuma 50% bi da bi. Na biyu, kimanta yawan tantanin halitta na PD-L1 magana ya bambanta dangane da nau'in ciwon daji. Misali, maganin ciwon sankara mai maimaitawa ko metastatic squamous cell carcinoma na kai da wuya na iya zabar yin amfani da wata hanyar gwajin da FDA ta amince da ita, Madaidaicin Mahimmanci (CPS). Abu na uku, kusan babu wata alaƙa tsakanin magana ta PD-L1 a cikin cututtukan daji daban-daban da kuma amsawar ICI, yana nuna cewa asalin ƙwayar cuta na iya zama babban mahimmancin tsinkayar alamun ICI. Misali, bisa ga sakamakon gwajin CheckMate-067, mummunan kimar tsinkayar magana ta PD-L1 a cikin melanoma shine kawai 45%. A ƙarshe, binciken da yawa sun gano cewa maganganun PD-L1 ba su da daidaituwa a cikin nau'o'in ciwon daji daban-daban a cikin majiyyaci guda ɗaya, har ma a cikin ƙwayar cuta guda ɗaya. A taƙaice, kodayake gwajin asibiti na farko na NSCLC ya haifar da bincike kan magana ta PD-L1 a matsayin mai yuwuwar tsinkayar halittu, amfanin aikin sa na asibiti a cikin nau'ikan ciwon daji daban-daban ya kasance ba a sani ba.

Nauyin maye gurbi. An yi amfani da Tumor Mutation Burden (TMB) azaman madadin mai nuna alamun rigakafi na ƙari. Dangane da sakamakon gwajin asibiti na KEYNOTE-158, daga cikin nau'ikan 10 na ci gaba da ci gaba da ciwace-ciwacen ciwace-ciwace da aka bi da su tare da pembrolizumab, marasa lafiya tare da aƙalla maye gurbi na 10 a kowace megabase (high TMB) suna da ƙimar amsa mafi girma fiye da waɗanda ke da ƙarancin TMB. Ya kamata a lura cewa a cikin wannan binciken, TMB ya kasance mai hangen nesa na PFS, amma ya kasa yin hasashen OS.

Amsar maganin rigakafi ya fi jan hankali ta hanyar sanin ƙwayoyin T na sababbin antigens. Tsarin rigakafi da ke da alaƙa da TMB mafi girma kuma ya dogara da dalilai daban-daban, ciki har da ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar cuta; Tsarin rigakafi yana gane ciwon neoantigens; Ikon mai watsa shiri don fara takamaiman martani na antigen. Misali, bayanai sun nuna cewa ciwace-ciwacen da ke da mafi girman kutsawa na wasu ƙwayoyin rigakafi na iya haƙiƙa suna da haɓakar haɓakar ƙwayoyin cuta na T cell (Treg). Bugu da ƙari, kewayon TMB na iya bambanta da yuwuwar TMB neoantigens, kamar yadda ainihin wurin maye gurbin ma yana taka muhimmiyar rawa; Maye gurbin da ke daidaita hanyoyin daban-daban na gabatarwar antigen na iya rinjayar gabatarwa (ko rashin gabatarwa) na sababbin antigens zuwa tsarin rigakafi, yana nuna cewa ƙwayar ƙwayar cuta da kuma halayen rigakafi dole ne su kasance daidai don samar da mafi kyawun amsawar ICI.

A halin yanzu, ana auna TMB ta hanyar jerin tsararraki na gaba (NGS), wanda zai iya bambanta tsakanin cibiyoyi daban-daban (na ciki) ko dandamalin kasuwanci da ake amfani da su. NGS ya haɗa da cikakken exome sequencing (WES), gabaɗayan jerin kwayoyin halitta, da jerin abubuwan da aka yi niyya, waɗanda za a iya samu daga ƙwayar ƙwayar cuta da ƙwayar ƙwayar cuta ta DNA (ctDNA). Yana da kyau a lura cewa nau'ikan ciwace-ciwace daban-daban suna da nau'ikan TMB masu yawa, tare da ciwace-ciwacen ƙwayoyin cuta kamar melanoma, NSCLC, da squamous cell carcinoma suna da matakan TMB mafi girma. Hakazalika, hanyoyin ganowa waɗanda aka ƙera don nau'ikan ƙari daban-daban suna da ma'anoni daban-daban na ƙimar ƙimar TMB. A cikin nazarin NSCLC, melanoma, urothelial carcinoma, da ƙananan ciwon huhu na huhu, waɗannan hanyoyin ganowa suna amfani da hanyoyi daban-daban na nazari (kamar gano WES ko PCR don takamaiman lambobi na kwayoyin halitta masu dangantaka) da ƙofa (TMB high ko TMB low).

Microsatellites ba su da kwanciyar hankali sosai. Microsatellite mai ƙarfi mara ƙarfi (MSI-H), azaman mai sarrafa kansar kwanon rufi don amsawar ICI, yana da kyakkyawan aiki a tsinkayar ingancin ICI a cikin cututtukan daji daban-daban. MSI-H shine sakamakon rashin daidaituwa na gyare-gyare (dMMR), wanda ke haifar da yawan maye gurbi, musamman a yankunan microsatellite, wanda ya haifar da samar da adadi mai yawa na sababbin antigens kuma a ƙarshe yana haifar da amsawar rigakafi na clonal. Saboda babban nauyin maye gurbi da dMMR ya haifar, ana iya ɗaukar ciwace-ciwacen MSI-H azaman nau'in ƙwayar ƙwayar cuta mai girma (TMB). Dangane da sakamakon gwajin asibiti na KEYNOTE-164 da KEYNOTE-158, FDA ta amince da pembrolizumab don maganin ciwace-ciwacen MSI-H ko dMMR. Wannan shi ne ɗayan magungunan ciwon daji na farko da FDA ta amince da su ta hanyar ilimin ƙwayoyin cuta maimakon ilimin tarihi.

Duk da gagarumar nasara, akwai kuma batutuwan da ya kamata ku sani yayin amfani da matsayin MSI. Alal misali, har zuwa 50% na dMMR marasa lafiya marasa lafiya ba su da amsa ga maganin ICI, yana nuna mahimmancin wasu siffofi a cikin tsinkayar amsa. Sauran abubuwan da suka shafi ciwace-ciwacen ciwace-ciwacen da ba za a iya tantance su ta hanyar dandamalin ganowa na yanzu na iya zama dalilai masu ba da gudummawa. Misali, an sami rahotannin cewa marasa lafiya tare da maye gurbi a cikin kwayoyin halittar da ke ɓoye mahimman abubuwan haɓakawa na polymerase delta (POLD) ko polymerase ε (POLE) a cikin yankin DNA ba su da amincin kwafi kuma suna nuna yanayin “super maye gurbin” a cikin ciwace-ciwacen su. Wasu daga cikin waɗannan ciwace-ciwacen sun ƙara haɓaka rashin kwanciyar hankali na microsatellite (don haka na MSI-H), amma sunadaran gyaran gyare-gyaren rashin daidaituwa ba su rasa (don haka ba dMMR ba).

Bugu da ƙari, kama da TMB, MSI-H kuma yana shafar sababbin nau'in antigen da aka haifar ta hanyar rashin zaman lafiya na microsatellite, amincewa da sababbin nau'in antigen, da karɓar tsarin rigakafi. Ko da a cikin nau'in ciwon sukari na MSI-H, an gano adadi mai yawa na maye gurbi na nucleotide a matsayin maye gurbin fasinja (ba maye gurbin direba ba). Sabili da haka, dogara kawai akan adadin microsatellites da aka gano a cikin ƙwayar cuta bai isa ba; Ainihin nau'in maye gurbi (wanda aka gano ta takamaiman bayanan bayanan maye gurbi) na iya haɓaka aikin tsinkaya na wannan mai alamar halitta. Bugu da kari, kadan ne kawai na masu fama da ciwon daji ke cikin ciwace-ciwacen MSI-H, wanda ke nuni da bukatar da ake da ita a yanzu na masu amfani da kwayoyin halitta. Sabili da haka, gano wasu masu tasiri masu tasiri don tsinkayar inganci da jagorancin kulawa da haƙuri ya kasance yanki mai mahimmanci na bincike.

Binciken tushen tsarin halitta

Ganin cewa tsarin aikin ICI shine ya sake juyar da kwayar cutar ta rigakafi maimakon kai tsaye kai tsaye ga hanyoyin da ke cikin ƙwayoyin tumor, ƙarin bincike ya kamata ya mayar da hankali kan nazarin yanayin ci gaban ƙwayar cuta da kuma hulɗar tsakanin ƙwayoyin tumo da ƙwayoyin rigakafi, wanda zai iya taimakawa wajen bayyana abubuwan da ke shafar amsawar ICI. Yawancin ƙungiyoyin bincike sun yi nazarin ciwace-ciwacen ƙwayoyin cuta ko sifofin rigakafi na takamaiman nau'ikan nama, irin su ƙari da sifofin maye gurbi na rigakafi, ƙarancin gabatarwar antigen tumor, ko cibiyoyin rigakafi da yawa ko tarawa (kamar sifofin lymphoid na uku), waɗanda zasu iya hasashen martani ga immunotherapy.

Masu bincike sun yi amfani da NGS don tsara ƙwayar ƙwayar cuta da ƙwayar rigakafi da kuma rubutun ƙwayoyin marasa lafiya kafin da kuma bayan jiyya na ICI, kuma sun gudanar da nazarin hoto na sararin samaniya. Ta yin amfani da ƙira mai yawa da aka haɗa, haɗe tare da dabaru irin su jerin tantanin halitta guda ɗaya da hoton sararin samaniya, ko ƙirar omics da yawa, an inganta iya hasashen sakamakon jiyya na ICI. Bugu da kari, wata cikakkiyar hanya don auna siginar rigakafi na ƙari da kuma halayen ƙwayar cuta na ciki shima ya nuna ƙarfin tsinkaya. Misali, cikakkiyar hanyar bin diddigin tsari wanda a lokaci guda ke auna kumburi da halayen rigakafi ya fi madaidaicin nazari guda ɗaya. Waɗannan sakamakon suna nuna wajibcin simulating ingancin ICI a cikin mafi fa'ida, gami da haɗa sakamakon kimantawa na ƙarfin garkuwar jiki, halayen ƙwayar cuta na ciki, da abubuwan rigakafi na ƙari a cikin marasa lafiya ɗaya don mafi kyawun hasashen wanda marasa lafiya zasu amsa ga immunotherapy.

Idan aka yi la’akari da rikiɗar haɗaɗɗun ƙwayar cuta da abubuwan masaukin baki a cikin binciken biomarker, da kuma yuwuwar buƙatar haɗin kai tsaye na sifofin microenvironment na rigakafi, mutane sun fara bincika masu gano ƙwayoyin cuta ta amfani da ƙirar kwamfuta da koyon injin. A halin yanzu, wasu nasarorin bincike masu fa'ida sun bayyana a wannan fanni, suna nuna makomar keɓaɓɓen ilimin cututtukan daji da ke taimakawa ta hanyar koyon injin.

Kalubalen da ke fuskantar masu tushen ƙwayoyin halitta

Iyakance hanyoyin nazari. Wasu ma'anoni masu ma'ana masu ma'ana suna yin kyau a wasu nau'ikan ƙari, amma ba lallai ba ne a cikin wasu nau'ikan ƙari. Ko da yake ƙayyadaddun nau'ikan ƙwayoyin ƙwayar cuta suna da ƙarfin tsinkaya fiye da TMB da sauransu, ba za a iya amfani da su don gano duk ciwace-ciwacen daji ba. A cikin binciken da aka yi niyya ga marasa lafiyar NSCLC, an gano sifofin maye gurbi sun fi tsinkayar ingancin ICI fiye da babban TMB (≥ 10), amma fiye da rabin marasa lafiya sun kasa gano fasalin maye gurbi.

Tumor iri-iri. Hanyar da ta dogara da ƙwayar nama kawai samfurori a wurin ƙwayar cuta guda ɗaya, wanda ke nufin kimanta takamaiman sassan ƙari bazai iya yin daidai daidai da bayanin duka ciwace-ciwacen da ke cikin majiyyaci ba. Alal misali, nazarin ya samo nau'i-nau'i a cikin maganganun PD-L1 tsakanin da kuma a cikin ciwace-ciwacen ƙwayoyi, kuma irin waɗannan batutuwa sun kasance tare da sauran alamun nama.

Saboda rikitaccen tsarin halitta, yawancin abubuwan da aka yi amfani da su a baya na iya zama mai sauƙi. Bugu da ƙari, ƙwayoyin sel a cikin ƙananan ƙwayoyin cuta (TME) yawanci suna wayar hannu, don haka hulɗar da aka nuna a cikin bincike na sararin samaniya bazai wakiltar ainihin hulɗar tsakanin ƙwayoyin tumo da ƙwayoyin rigakafi ba. Ko da masu nazarin halittu za su iya wakiltar duk yanayin ƙwayar cuta a wani takamaiman lokaci, ana iya haifar da waɗannan maƙasudin kuma suna canzawa cikin lokaci, yana nuna cewa hoto ɗaya a lokaci ɗaya bazai wakiltar canje-canje masu ƙarfi da kyau ba.

Bambance-bambancen haƙuri. Ko da an gano canje-canjen da aka sani game da juriya na ICI, wasu marasa lafiya da ke ɗauke da sanannun magungunan ƙwayoyin cuta na iya ci gaba da amfana, watakila saboda kwayoyin halitta da / ko na rigakafi da ke cikin ƙwayar cuta da kuma a wurare daban-daban. Misali, rashi na β 2-microglobulin (B2M) na iya nuna sabon juriya ko samu, amma saboda bambancin rashi na B2M tsakanin daidaikun mutane da kuma cikin ciwace-ciwace, da kuma hulɗar hanyoyin maye gurbin rigakafi a cikin waɗannan marasa lafiya, ƙarancin B2M na iya ƙi yin hasashen juriya na mutum ɗaya. Sabili da haka, duk da kasancewar rashi na B2M, marasa lafiya na iya ci gaba da amfana daga maganin ICI.

Alamar rayuwa mai tsayi ta tsari
Maganar masu amfani da kwayoyin halitta na iya canzawa a tsawon lokaci kuma tare da tasirin magani. Ƙididdigar ƙima da guda ɗaya na ciwace-ciwacen ƙwayoyi da immunobiology na iya yin watsi da waɗannan canje-canje, kuma ana iya yin watsi da canje-canje a cikin ƙwayar cuta TME da matakan amsawar rigakafi. Yawancin karatu sun nuna cewa samun samfurori kafin da kuma lokacin jiyya na iya gano ainihin canje-canjen da suka shafi jiyya na ICI. Wannan yana nuna mahimmancin ƙima mai ƙarfi na biomarker.

Abubuwan da ke tushen jini
Amfanin nazarin jini ya ta'allaka ne a cikin iyawar ilimin halitta don kimanta duk raunin ciwon daji na mutum, yana nuna matsakaicin karatu maimakon takamaiman karatun rukunin yanar gizon, yana mai da shi musamman dacewa don kimanta canje-canje masu ƙarfi da suka shafi jiyya. Sakamakon bincike da yawa sun nuna cewa yin amfani da DNA na ƙwayar cuta (ctDNA) ko ƙwayoyin ƙwayar cuta (CTC) don kimanta ƙananan cututtuka (MRD) na iya jagorantar shawarwarin jiyya, amma waɗannan gwaje-gwajen suna da iyakacin bayanai game da tsinkaya ko marasa lafiya zasu iya amfana daga maganin rigakafi kamar ICI. Don haka, gwajin ctDNA yana buƙatar haɗawa tare da wasu hanyoyin don auna kunnawar rigakafi ko ɗaukar nauyin rigakafi. Dangane da wannan, an sami ci gaba a cikin rigakafin rigakafi na ƙwayoyin jini guda ɗaya (PBMCs) da kuma nazarin ƙwayoyin cuta na vesicles na waje da plasma. Misali, subtypes na rigakafi na gefe (irin su CD8+T Kwayoyin), babban magana na ƙwayoyin cuta masu bincikar rigakafi (kamar PD1 akan ƙwayoyin CD8+T na gefe), da haɓakar matakan sunadarai daban-daban a cikin plasma (kamar CXCL8, CXCL10, IL-6, IL-10, PRAP1, da VEGFA) na iya yin tasiri ga duk abubuwan da suka dace. Amfanin waɗannan sababbin hanyoyin shine za su iya kimanta canje-canje a cikin ƙwayar cuta (kamar sauye-sauyen da ctDNA ta gano) kuma suna iya bayyana canje-canje a cikin tsarin rigakafi na mai haƙuri.

Radiomics
Abubuwan tsinkaya na bayanan hoto na iya shawo kan iyakokin samfurin biomarker na nama da biopsy yadda ya kamata, kuma suna iya lura da ciwace-ciwacen ciwace-ciwacen daji da sauran wuraren metastatic a kowane lokaci. Saboda haka, za su iya zama wani muhimmin ɓangare na masu amfani da kwayoyin halitta marasa lalacewa a nan gaba. Delta radiomics na iya ƙididdige canje-canje a cikin fasalulluka masu yawa (kamar girman ƙari) a wurare daban-daban, kamar kafin da bayan jiyya na ICI, yayin jiyya, da kuma biyo baya. Delta radiomics ba zai iya hango hasashen farko ko rashin amsawa ga jiyya da wuri ba, amma kuma sun gano juriya da aka samu ga ICI a cikin ainihin lokaci kuma suna lura da duk wani maimaitawa bayan cikakkiyar gafara. Samfurin hoto da aka haɓaka ta hanyar fasahar koyan na'ura ya fi ma'auni na RECIST na al'ada wajen tsinkayar amsawar jiyya da abubuwan da suka faru mara kyau. Bincike na yanzu yana nuna cewa waɗannan samfuran rediyo suna da yanki a ƙarƙashin lanƙwasa (AUC) har zuwa 0.8 zuwa 0.92 a cikin tsinkayar amsawar rigakafin rigakafi.

Wani fa'idar radiomics shine ikonsa na tantance ci gaban pseudo daidai. Samfurin rediyo da aka gina ta hanyar koyon injin na iya bambanta sosai tsakanin ci gaba na gaskiya da na ƙarya ta hanyar sake auna bayanan CT ko PET ga kowane ƙari, gami da abubuwa kamar sura, ƙarfi, da rubutu, tare da AUC na 0.79. Ana iya amfani da waɗannan ƙirar rediyo a nan gaba don guje wa ƙarewar jiyya da wuri saboda kuskuren ci gaban cuta.

Microbiota na hanji
Ana sa ran alamomin halittu na gut microbiota suyi tsinkaya martanin warkewa na ICI. Yawancin karatu sun nuna cewa takamaiman microbiota na gut yana da alaƙa da martani na nau'ikan ciwon daji daban-daban zuwa maganin ICI. Alal misali, a cikin marasa lafiya tare da melanoma da ciwon hanta, yawancin kwayoyin Ruminococcaceae suna da alaƙa da amsawar immunotherapy PD-1. Akkermansia muciniphila haɓakawa ya zama ruwan dare a cikin marasa lafiya masu ciwon hanta, ciwon huhu, ko carcinoma na renal cell, waɗanda ke amsa da kyau ga maganin ICI.

Bugu da kari, sabon samfurin koyon injin zai iya zama mai zaman kansa daga nau'ikan ƙari kuma yana haɗa takamaiman nau'in ƙwayoyin cuta na gut tare da amsawar warkewa na rigakafi. Sauran nazarin kuma sun bayyana takamaiman rawar da ƙungiyoyin ƙwayoyin cuta guda ɗaya ke takawa wajen daidaita tsarin garkuwar jiki, tare da ƙara nazarin yadda za a kare ko inganta kubucewar ƙwayoyin cutar kansa.

Neoadjuvant far
Ƙididdigar ƙima mai ƙarfi na ilimin halitta na ƙari zai iya jagorantar dabarun jiyya na asibiti na gaba. Gwajin maganin neoadjuvant na iya ƙididdige tasirin warkewa ta hanyar cututtukan cututtuka a cikin samfuran tiyata. A cikin maganin melanoma, amsawar farko ta farko (MPR) tana da alaƙa da sake dawowa da ƙimar rayuwa kyauta. A cikin gwaji na PRADO, masu bincike sun ƙayyade matakan shiga tsakani na gaba na asibiti, irin su tiyata da/ko maganin jiyya, dangane da ƙayyadaddun bayanan gafartawa marasa lafiya.

Daga cikin nau'o'in ciwon daji daban-daban, yawancin sababbin hanyoyin maganin adjuvant har yanzu basu da kwatancen kai da kai. Sabili da haka, zaɓi tsakanin immunotherapy monotherapy ko haɗin haɗin gwiwa sau da yawa ana yanke shawara tare da likitan halartar da majiyyaci. A halin yanzu, masu bincike sun haɓaka fasalin gamma na interferon (IFN gamma) wanda ke ɗauke da kwayoyin halitta 10 a matsayin mai ƙididdigewa don tsinkayar gafarar cututtuka a cikin melanoma bayan maganin neoadjuvant. Sun ƙara haɗa waɗannan fasalulluka a cikin algorithm don zaɓar marasa lafiya tare da ƙarfi ko raƙuman martani ga jiyya na neoadjuvant. A cikin binciken da aka biyo baya da ake kira DONIMI, masu bincike sunyi amfani da wannan maki, tare da ƙarin bincike mai mahimmanci, ba kawai don tsinkayar amsawar jiyya ba, amma kuma don sanin wane mataki na III marasa lafiya na melanoma suna buƙatar ƙarin haɓakar histone deacetylase inhibitors (HDACi) don haɓaka amsawa ga neoadjuvant ICI magani.

Tumor model samu daga marasa lafiya
Samfuran ƙwayar ƙwayar cuta a cikin vitro suna da yuwuwar hasashen takamaiman martanin haƙuri. Ba kamar dandamalin in vitro da aka yi amfani da shi don nazarin bakan maganin miyagun ƙwayoyi game da cutar cututtukan jini ba, ciwace-ciwacen ciwace-ciwace suna fuskantar ƙalubale mafi girma saboda ƙayyadaddun ƙayyadaddun ƙwayar ƙwayar ƙwayar cuta da kuma hulɗar rigakafin ƙwayar cuta. Sauƙaƙan al'adar ƙwayar ƙwayar cuta ba za ta iya yin kwafin waɗannan hadaddun fasali cikin sauƙi ba. A wannan yanayin, ƙari kamar gabobin jiki ko guntuwar gabobin da suka samo asali daga marasa lafiya na iya ramawa ga waɗannan iyakokin tsarin, saboda suna iya adana ainihin tsarin ƙwayar ƙwayar cuta da kuma daidaita hulɗa tare da ƙwayoyin rigakafi na lymphoid da myeloid don kimanta martanin ICI a cikin takamaiman yanayin haƙuri, ta haka ne ya fi dacewa da sake haifar da sifofin halittu a cikin ingantaccen yanayi mai girma uku.

Nazari da dama na ci gaba a China da Amurka sun yi amfani da wannan sabon tsarin aminci mai girma uku mai girma a cikin in vitro. Sakamakon ya nuna cewa waɗannan samfuran za su iya yin hasashen martanin cutar kansar huhu, ciwon hanji, ciwon nono, melanoma da sauran ciwace-ciwace zuwa ICI. Wannan yana kafa tushe don ƙara tabbatarwa da daidaita aikin hasashen waɗannan samfuran.