Mhlawumbi i-immune system izisa iingcinga zeeseli ezimhlophe zegazi ezixubha kwiibhaktheriya, okanye iintsholongwane ezihlasela umhlasela-kwamanye amazwe-ezi zikhusela umzimba wakho kwiibhaktheriya kunye neentsholongwane ezinokukugula. Nangona kunjalo, i-immune system iyaziwa ngokukwazi kwayo ukubona, ukufuna, nokutshabalalisa iiseli zomhlaza.
Ngamandla anjalo njengamandla omzimba, kufuneka kube yindlela yokudayela izinto phantsi kwenotshi ukwenzela ukuba iifestile eziqhelekileyo, ezempilo azihlaselwa ngephutha.
Ngethamsanqa, isistim somzimba sisilwe ngolu vavanyo lwezokhuseleko kwindawo. Nangona kunjalo, iiseli zomhlaza, ezivela kwiiseli ezaziqhelekileyo, ngamanye amaxesha zingasebenzisa ukuhlolwa kwezokhuseleko kumsebenzi wazo ukuphepha ukuhlaselwa ngumzimba wokuzivikela. Ezi zokuhlola (ukhuselo, ngokwenene) ziyaziwa ngokwesayensi njengendlela yokuhlola , kwaye iziyobisi ezithatha ama-checkpoints are inhibitors.
Iimpawu zokuHlola
Njengazo iinkqubo ezibalulekileyo kwishishini kunye nokusebenza, isigqibo somzimba sokutshisa impendulo yokuzivikela ngomzimba kaninzi sidinga "amanqaku" kunye "nokuvunywa" ngaphambi kokuba iivili zibekwe inzame-ngalinye isebe linakho okanye lingenalo isisindo esifanayo kunye Isebe alisoloko lifuna isigqibo.
Ngaloo ndlela, izikhuselo ezininzi ezikhuselekileyo zinceda ukugcina isimiso somzimba sokuzikhusela sisigxininise kwi-invader yangaphandle okanye ukuphazamisa isigaba "sobuntu" somhlaseli onobungozi. Ezi khuselo zingasetyenziselwa ngokunyamekela ngamaseli omhlaza ukuze ziphephe ukufunyanwa komzimba kodwa ziyakuthi zitshintshwe ngabaphuhlisi beziyobisi ukuba baye kwiiseli zomhlaza ze-uncloak ukuze "bangabonakali" kumzimba womzimba .
Esi sigqibo soshishino se-biologism sokuphakamisa iimpendulo zomzimba ngamanye amaxesha kubalulekile kubandakanya ukulungelelaniswa kunye "neli sebe lokufa kweselingo" -kuthi, ukufa okucwangcisiweyo 1 (PD-1) indlela elawula izimpendulo zokuvuvukala kwezicubu.
I-Inhibitors yokuHlola i-Drugs ukunceda i-T cell i-Order Ordering Orders
Umzila we-PD-1 unomgca othe ngqo kumaseli e-T, amasosha omzimba aphuma kwaye abulale amangqamuzana omhlaza; Nangona kunjalo, kukude kwinto eqinisekileyo ukuba i-cell cell yaseT-cell iyaziququlela ngokwawo, yenze phambili, ize iqalise ukutshabalalisa iiseli zomhlaza.
Kungenxa yokuba amanye amasebe anomdla kwiT-cell kunye nemisebenzi yabo. Kukho amanqaku amaninzi okumelwe ukuba ayenze phambi kokuba amajoni athole imiyalelo yokuhamba.
Enye yezinto ezichonga ukuba ngaba iilawuni zokuhamba zihanjiswa yi-receptor ye-PD1, ekhonza uhlobo oluthile oluqhelekileyo kwi-chain of command. Ababini "abacebisi" kulo mgaqo jikelele ocebisa kakhulu ukuchasa imfazwe ngamaseli omhlaza yi-PDL-1 kunye ne-PDL-2. Abacebisi abachasile imfazwe, i-PDL-1 kunye ne-PDL-2, ngokwenene iimoleksi ezibophelela kwi-PD1 receptors kwiT-cell. Xa bebopha ba xelela iiseli ze-T ukuba zime phantsi, ezingenayo imiyalelo yokuhamba ngomdlavuza.
Iisetyana zeCans May zingamazama ukuvelisa "Abacebisi beMfazwe"
Ngamanye amaxesha iiseli zomhlaza zenza abacebisi abaninzi bemfazwe-mfa, ngokwabo. Omnye okanye bobabini be-PD-L1 kunye ne-PD-L2, kwiiseli kwiifom, kuquka namaseli omhlaza, angabophela kwi-PD1 receptors kwi-T-seli kunye nokuvimbela umsebenzi wabo.
Ukuthintela ukusebenzisana phakathi kwe-PD-1 kwiT-iiseli kunye nabadlali bayo ababini, ophezu kwamanye amaseli, kunokubangela ukuba kusebenze ngamandla kwee-T, kunye neengqungquthela yeziganeko ezibangelwa ukuphendula okukhawulezayo.
Unyango olujolise kwi-PD-1 okanye i-PD-L1
Ezinye iiseli zomhlaza zivelisa inani elikhulu le-PD-L1, elinceda babalekele ukuhlaselwa ngumzimba.
Abaphandi bezophuhliso beziyobisi bangenza unyango lwama-antioclonal antibody olujolise okanye i-receptor ye-PD-1 (jikelele) okanye i-ligand ye-PD-L1 (umcebisi-mlwaphulo-mkhosi) ukukhuthaza ukukhuselana nomzimba kunye nomhlaza wesifo, kwaye sele isetyenziswe ekuphatheni i cancer.
Ekuqaleni, impumelelo yabonakala ngokuxhamla, kodwa ngoku iinjongo zicutshungulwa kwi-hematologic cancers, okanye i- blood cancer , kunye ne-leukemia, i-lymphoma kunye ne-myeloma. Kwi-Hodgkin lymphoma yeklasini, kukho ukwanda kwe-PD-1 ligand (PD-L1 / 2) kwimveliso yamaseli omhlaza kangangokuba kukho ithemba malunga nokukhuselwa kwe-Hodgkin lymphoma kwi-PD-1 yokukhusela.
Ekubeni ezo zonyango zikhuthaza umzimba wokuzikhusela ngokukhupha ezinye zokukhuselwa kwazo, kukho ukukhathazeka ukuba oku kungakhokelela ekulimaleni kwiseli ezinempilo kunye nemiphumo echaphazelekayo kwabanye abantu. Iziganeko ezimbi eziqhelekileyo ezidibaniswa nama-antibodies ezi-P-1-block block zibandakanya ukutshabalalisa, ukugqithisa, kunye nehudo. Ngaphantsi kaninzi banokubangela iingxaki ezinzulu kwimiphunga, emathunjini, esibindi, ezintsweni, kwiingqungquthela zokwenza i-hormones, okanye ezinye izitho.
Ezinye iindlela ezininzi zonyango ezijoliswe ku-PD-1 okanye i-PD-L1 ngoku zivavanywa kwizilingo zeclini, kunye zombini kunye kunye nezinye iziyobisi. Zimbalwa zezi zonyango ezifumene imvume ye-FDA yokusetyenziswa ngomhlaza ngoku, kodwa abanye abaninzi ngoku bafundiswa kwizilingo zeclini. Njengoko uphando luqhubeka, siya kuqonda kakuhle inkqubo nendlela yokufumana ukulawula ngayo.
> Imithombo:
Ansell SM, Lesokhin AM, Borrello I, et al. I-PD-1 i-Blockade kunye neNivolumab ekubuyiselweni kwakhona okanye kwi-Lymphoma ye-Refractory. N Engl J Med. 2015; 372 (4): 311-319.
Pardoll DM. Ukukhutshwa kweengcambu zokuzikhusela kumzimba kumhlaza we-immunotherapy. Nat Rev Cancer. 2012; 12 (4): 252-64.
I-Romano E, uRomero P. Isithembiso sokuthintela ukuphazamisa isikhokelo somzimba we-PD-1 / PD-L1 emdlalweni: ukukhutshwa komsebenzi we-CD8 T we-cell mediated anti-tumor kuphumela ekusebenzeni okuphawulekayo, okungazange kwenzeke ngeklinikhi kwiimpawu ezihlukahlukeneyo ezinamandla. J Omnye umdlavuza . 2015; 3: 15.
American Cancer Society. I-immune checkpoint inhibitors ukunyanga umdlavuza.