Ukuvuvukala okungapheli kungabangela izinhlobonhlobo zezimila eziyingozi kuhlanganise nomdlavuza wesibindi. Phambilini, bekukholelwa ukuthi ukuvuvukala kuthinta ngqo amangqamuzana e-tumor futhi kukhuthaze ukuhlukaniswa kwawo ukuze awavikele ekufeni. IYunivesithi yaseCalifornia, iSan Diego Michael Karin nabanye bathola ukuthi isifo sokusha kwesibindi kohlobo esingalapheki sivusa umdlavuza wesibindi ngokucindezela ukubhekwa kwamasosha omzimba. (Imvelo. 2017 Nov 08. doi: 10.1038 / nature24302)
Recently, immunotherapy represented by immune checkpoint inhibitors and adoptive T-cell therapy has achieved great success in isisu treatment. Prompt the significant effect of activated immune cells to eradicate tumors, but now we have not taken the role of immune surveillance or adaptive immunity in tumorigenesis seriously. This study provides the most powerful and direct evidence to support adaptive immunity to actively prevent umdlavuza wesibindi.
Abacwaningi abazange basebenzise imodeli yegundane elenziwe ngobunjiniyela elivamile, kodwa imodeli yegundane etholakala endleleni yemvelo ye-non-alcoholic steatohepatitis (NASH). Lesi simila sifana kakhulu nomdlavuza wesibindi somuntu. I-NASH yisifo sesibindi esiqhubekayo esibangelwa ukunqwabelana kwamafutha esibindini. Kungabangela ukulimala kwesibindi, i-fibrosis, kanye nenani elikhulu lokuguqulwa kofuzo, okuholela ku-cirrhosis, ukwehluleka kwesibindi, kanye ne-hepatocellular carcinoma.
Ucwaningo lwathola ukuthi ukuguqulwa kwezakhi zofuzo ezihlobene ne-NASH kungashukumisa isimiso somzimba sokuzivikela ezifweni, kuhlanganise namangqamuzana e-cytotoxic T, ukuze abone futhi ahlasele amangqamuzana e-tumor avelayo; Nokho, kubantu namagundane, i-hepatitis engapheli iphinde ibangele ukunqwabelana kwamaseli e-immunosuppressive lymphocyte IgA + .
Empini yamangqamuzana amabili omzimba omzimba, amaseli e-IgA + namaseli e-cytotoxic T, ama-lymphocyte avikelayo anqobayo. Amaseli e-IgA + aveza i-Programmed Death Ligand 1 (PD-L1) ne-interleukin-10, futhi avimbela ngokuqondile ama-lymphocyte e-hepatotoxic CD8 + T nge-PD-L1. Ngemva kokucindezelwa kwama-T cell, amathumba esibindi akheka futhi akhule kumagundane e-hepatitis angapheli .
Ukwengeza, phakathi kwamagundane angu-15 angenayo i-anti-tumor cytotoxic T cell, i-27% yamagundane ahlakulela izimila ezinkulu zesibindi ezinyangeni ze-6, futhi akukho neyodwa yamagundane anamaseli e-cytotoxic T anezimila. Cishe asikho isimila kumagundane angenayo i-immunosuppressive lymphocyte, okuphakamisa ukungabikho kwamaseli e-IgA +, ukuze amaseli e-cytotoxic T adedelwe ukuze aqedele umphumela wokulwa nesimila.
I-PD-L1 inomphumela wokwenza i-immunosuppressive lymphocyte icindezele amaseli e-cytotoxic T, okuveza ubuthakathaka balolu hlelo lokusebenza. Lapho abacwaningi basebenzisa izidakamizwa noma ubunjiniyela bezakhi zofuzo ukuvimbela i-PD-L1, amaseli e-IgA + akhishwa esibindini. Amaseli e-T anobuthi avuselelwe adlala indima ekuqedeni izimila. Lokhu kunikeza ukusekelwa kwethiyori ukuvimba i-PD-L1 ngezidakamizwa ze-PD-1 inhibitor ezingadala ukuhlehla komdlavuza wesibindi. Ilungu lokuqala laleli qembu lezidakamizwa, i-nivolumab, lisanda kugunyazwa ukwelapha i-advanced hepatocellular carcinoma. Abacwaningi bacwaninga ukuthi amaseli e-IgA + ahlanganiswa kanjani esibindini, benethemba lokuthola izindlela zokuphazamisa ukunqwabelana noma ukukhiqizwa kwala mangqamuzana, futhi banikeze imibono emisha yokuvimbela noma yokwelapha kusenesikhathi umdlavuza wesibindi.
I-nivolumab ka-Bristol-Myers Squibb (Nivolumab, Opdivo) yagunyazwa yi-US FDA ngoSepthemba kulo nyaka ezigulini ze-hepatocellular carcinoma ngemva kokwelashwa kwe-sorafenib, ibe eyokuqala nokuwukuphela kwe-FDA egunyazwe kulesi sibonakaliso Semithi elwa nesimila sokuzivikela komzimba.
Njengamanje, ama-PD-1 inhibitors afaka i-Pembrolizumab (Keytruda), i-AstraZeneca's Durvalumab (Imfinzi), BeiGene BGB-A317, i-Hengrui's SHR-1210, njll. Izivivinyo zomtholampilo zokwelashwa komdlavuza wesibindi ziyaqhubeka.
