Mumakore achangopfuura kwave nekuwedzera kwekurapwa kwegomarara kunonangana nehurongwa hwekudzivirira zvirwere. Parizvino, marapirwo aya haana kushanda mukurapa osteosarcoma (OS). Vatsvakurudzi vave kuedza kunzwisisa kuti sei marapirwo aya asiri kushanda.
Ichangopfuura kudzidza akatarisa OS tumor microenvironment pane imwechete sero level. Izvi zvinoreva kutarisa masero ega ega akakomberedza bundu. Izvi zvinosanganisira masero ezvirwere. Chinangwa chechidzidzo ichi chaive chekupa nzwisiso yemamiriro ekudzivirira eOS uye nekugona kujekesa kuti inganange sei nemishonga.
Chikwata chakaongorora OS RNA yekuteedzera data kubva kumarekodhi akamboburitswa. RNA sequencing inyanzvi inotitaurira kuti ndeapi majini anobatidzwa kana kudzimwa mumaseru. Kuita izvi pachikamu chimwe chete chesero (panzvimbo pebundu rose) kunotibvumira kuziva zviri kuitika musero rega rega. Izvi zvakakosha nekuti mamota akaomarara uye anoumbwa nemhando dzakasiyana siyana dzemasero. "Mepu" inogona kugadzirwa kubva ku RNA kutevedza data, panoiswa sero rimwe nerimwe zvichibva pakuti magene anobatidzwa musero iroro. Rudzi rwesero runogona kuzivikanwa zvichienderana nekuti ndeapi majini akawanikwa. Masero ane majini akafanana akabatidzwa achange ari pedyo nerimwe pamepu. Pamepu iyi, vaongorori vakawana akati wandei akasiyana masero edziviriro mu tumor microenvironment.
Masero eDendritic
Dendritic masero imhando yemasero anodzivirira muviri 'anotarisa' muviri kune zvinhu zvisingafanirwe kunge zviripo. 'Vanonhonga' zvidimbu zvezvinhu zvekune dzimwe nyika zvinonzi maantigen uye vozviratidza kune mamwe masero edziviriro yezvirwere kuti aite kuti immune system iite. Izvi zvinogona kurwisa chirwere chinotapukira (semuenzaniso hutachiona, bhakitiriya, fungus) kana sero regomarara.
Kune marudzi akawanda emasero edendritic. Kuburikidza nekuongorora iyo RNA yekuteedzera data vaongorori vakawana subset yemasero edendritic, anonzi mregDCs, ayo aive akajairika muOS tumor microenvironment kupfuura munyama yakatenderedza. Vatsvakurudzi vakabva vaongorora zvavaiita. Vakaona kuti masero edendritic anogona kunge achitora anodzora T masero (Tregs) kune bundu microenvironment. Tregs inodzvinyirira immune system. Izvi zvinogadzira nharaunda umo mapundu anogona kukura zviri nyore. Kunyangwe tsvakiridzo yakawanda yemaitiro emamregDCs inodiwa, chidzidzo chekutanga ichi chinoratidza kuti chingave nebasa rekuunza mamwe masero ekudzivirira zvirwere mukati mebundu microenvironment.
Masero ane MHC kirasi I
MHC kirasi I mamorekuru chimwe chikamu che immune system. Anowanikwa pamusoro pemasero akawanda emumuviri. Vanogona kuunza maantigen kune mamwe maseru ekudzivirira, achimutsa mhinduro yekudzivirira.
Ichi chidzidzo chakawana kuti mazinga eMHC kirasi I akaderedzwa mumhando yepamusoro-giredhi OS maseru. Izvi zvakaonekwa zvese muRNA yekuteedzera data uye pavakatarisa OS tumor samples. Zvinogoneka kuti kudzikiswa kwekirasi yeMHC ini ndaigona kubatsira masero eOS kunzvenga mhinduro yekudzivirira.
Macrophage
Macrophage masero anodzivirira zvirwere ane mabasa akati wandei mumuviri. Vanochenesa masero akafa, vanokurudzira mamwe masero emuviri uye vanogona 'kudya' zvinhu zvisingafanirwe kunge zviripo kusanganisira maseru egomarara.
Macrophages anowanzoonekwa mune OS tumor microenvironment. Nekudaro, muOS macrophages haagare achidya cancer maseru uye mamwe macrophages anogona kunge ari kubatanidzwa mukubatsira masero eOS kunzvenga immune system.
Ichi chidzidzo chakaongorora kuti sei macrophages angave 'asingadye' OS masero. Vatsvakurudzi vakatarisa zvakananga kuCD24, chiratidzo chinowanikwa pamusoro pemasero, anozivikanwa kutumira 'usandidye' zviratidzo kune macrophages. Ongororo yedata yakaratidza kuti CD24 yaigara 'yakabatidzwa' mumaseru eOS zvichienzaniswa nemaseru akatenderedza. Vatsvagiri vakaongorora basa reCD24 muOS. Chekutanga, vakaongorora mhedzisiro yaive neCD24 paOS cell mitsara (masero anorimwa murabhoritari). Vakaona kuti kana kutaura kweCD24 kwakaderedzwa macrophages aive akanyanya kushanda. Vakabva vatarisa kuti vaone kana vaive nemhinduro imwechete mumamodheru emakonzo. CD24 payakaderedzwa mumhando idzi mamota haana kukura nekukurumidza. Vachitarisa mabundu padhuze vakawana zvakare kuti kudzikisa CD24 mumakonzo modhi kwakawedzera huwandu uye kuita kwemaseru edziviriro panzvimbo yebundu. Izvi zvaisanganisira macrophages. Mhedzisiro iyi inoratidza kuti masero eOS anogona kudzivirira macrophages kuburikidza nechiratidzo cheCD24. Naizvozvo, kuvhara CD24 kunogona kuwedzera mukana we macrophages kuparadza maseru egomarara.
Zvese zvakawanikwa izvi ndiwo matanho ekutanga muhurongwa hwekutsvagisa. Ivo vanopa yekutanga chitubu chekuongorora iyo OS immune nharaunda zvakare. Isu tinotarisira kuona zvimwe zvidzidzo zvinotarisa pakunzwisisa kuti OS inonzvenga sei immune system. Kubva ipapo tinokwanisa kuwana mishonga mitsva inonangwa nekugadzira mishonga mitsva