nūhou

Ua lawe mai ka Immunotherapy i nā loli hou i ka mālama ʻana i nā maʻi maʻi ʻino, akā aia kekahi mau maʻi ʻaʻole hiki ke pōmaikaʻi. No laila, makemake nui ʻia nā biomarkers kūpono i nā noi lapaʻau e wānana i ka maikaʻi o ka immunotherapy, i mea e hoʻonui ai i ka pono a pale i nā mea ʻawaʻawa pono ʻole.

Ua ʻae ʻia nā biomarkers FDA

Hōʻike PD-L1. ʻO ka loiloi ʻana o nā pae hōʻike PD-L1 e ka immunohistochemistry (IHC) e hāʻawi i ka helu ʻai ʻana o ka tumo (TPS), ʻo ia ka pākēneka o nā pūnaewele ʻokoʻa ʻāpana a i ʻole membrane piha o kēlā me kēia ikaika i ke ola ʻana o nā pūnaewele tumo. I loko o nā hoʻokolohua lapaʻau, lawelawe kēia hoʻokolohua ma ke ʻano he hoʻāʻo diagnostic auxiliary no ka mālama ʻana i ka maʻi maʻi maʻi maʻi ʻaʻole liʻiliʻi liʻiliʻi (NSCLC) me ka pembrolizumab. Inā ≥ 1% ka TPS o ka hāpana, manaʻo ʻia ka ʻōlelo PD-L1; Hōʻike ka TPS ≥ 50% i ka hōʻike kiʻekiʻe o PD-L1. I ka ho'āʻo mua o ka Phase 1 (KEYNOTE-001), ʻo 45.2% ka pane pane o nā mea maʻi ma ka PD-L1 TPS> 50% me ka hoʻohana ʻana i ka pembrolizumab, ʻoiai me ka nānā ʻole o TPS, ʻo ka pane pane o nā maʻi āpau e loaʻa ana i kēia mālama ʻana i ka immune checkpoint inhibitor (ICI) he 19.4%. ʻO ka hoʻāʻo 2/3 ma hope (KEYNOTE-024) i hāʻawi ʻia i nā maʻi me PD-L1 TPS> 50% e loaʻa i ka pembrolizumab a me ka chemotherapy maʻamau, a ua hōʻike nā hopena i kahi hoʻomaikaʻi nui i ke ola holoʻokoʻa (OS) i nā maʻi e loaʻa ana i ka mālama pembrolizumab.

Eia naʻe, ʻo ka noi ʻana o PD-L1 i ka wānana ʻana i nā pane ICI i kaupalena ʻia e nā kumu like ʻole. ʻO ka mea mua, ʻokoʻa ka paepae kūpono no nā ʻano maʻi maʻi like ʻole. No ka laʻana, hiki ke hoʻohana ʻia ʻo Pabolizumab i ka wā o ka hōʻike ʻana o ka maʻi maʻi PD-L1 o nā mea maʻi me ka maʻi maʻi ʻōpū, ka maʻi ʻaʻai esophageal, ka maʻi maʻi maʻi ʻaʻai a me ka maʻi ʻāʻī he 1%, 10% a me 50%. ʻO ka lua, ʻokoʻa ka loiloi ʻana i ka heluna cell o ka ʻōlelo PD-L1 ma muli o ke ʻano o ka maʻi kanesa. No ka laʻana, hiki i ka mālama ʻana i ka maʻi maʻi maʻi squamous cell hou a i ʻole metastatic o ke poʻo a me ka ʻāʻī ke koho e hoʻohana i kahi ala hoʻāʻo ʻē aʻe i ʻae ʻia e FDA, ʻo ka Comprehensive Positive Score (CPS). ʻO ke kolu, aneane ʻaʻohe pilina ma waena o ka ʻōlelo PD-L1 i nā maʻi maʻi like ʻole a me ka pane ʻana o ICI, e hōʻike ana he kumu nui ke kumu o ka wanana ICI biomarkers. No ka laʻana, e like me nā hopena o ka hōʻike ʻo CheckMate-067, ʻo ka waiwai wānana maikaʻi ʻole o ka ʻōlelo PD-L1 i ka melanoma he 45% wale nō. ʻO ka hope, ua ʻike ʻia nā haʻawina he nui ʻaʻole kūlike ka ʻōlelo PD-L1 ma waena o nā maʻi maʻi ʻokoʻa i loko o ka maʻi hoʻokahi, ʻoiai i loko o ka maʻi maʻi like. I ka hōʻuluʻulu ʻana, ʻoiai ʻo nā hoʻokolohua lapaʻau mua o NSCLC i hoʻoikaika i ka noiʻi ʻana i ka ʻōlelo PD-L1 ma ke ʻano he biomarker hiki ke wānana, ʻaʻole maopopo ka pono o ka maʻi lapaʻau i nā ʻano maʻi kanesa.

ʻO ke kaumaha o ka hoʻololi ʻana i ke koko. Ua hoʻohana ʻia ʻo Tumor Mutation Burden (TMB) ma ke ʻano he hōʻailona ʻē aʻe o ka immunogenicity tumor. Wahi a nā hopena hoʻokolohua lapaʻau o KEYNOTE-158, ma waena o nā ʻano maʻi maʻi paʻa kiʻekiʻe he 10 i mālama ʻia me ka pembrolizumab, ʻo nā mea maʻi me ka liʻiliʻi he 10 mau hoʻololi i kēlā me kēia megabase (TMB kiʻekiʻe) ʻoi aku ka nui o ka pane pane ma mua o ka poʻe me ka TMB haʻahaʻa. He mea pono e hoʻomaopopo i kēia haʻawina, ʻo TMB kahi wānana o PFS, akā ʻaʻole hiki iā ia ke wānana i ka OS.

ʻO ka pane ʻana o ka immune therapy e alakaʻi nui ʻia e ka ʻike cell T o nā antigens hou. ʻO ka immunogenicity e pili ana me ka TMB kiʻekiʻe e pili pū ana i nā kumu like ʻole, me ka neoantigen tumor i hōʻike ʻia e ka ʻōpū; Hoʻomaopopo ka ʻōnaehana pale i nā neoantigens tumor; ʻO ka hiki o ka mea hoʻokipa ke hoʻomaka i nā pane antigen-specific. No ka laʻana, hōʻike ʻia ka ʻikepili e loaʻa maoli i nā ʻōpū me ka infiltration kiʻekiʻe loa o kekahi mau cell immune. Eia kekahi, ʻokoʻa paha ka laulā o ka TMB mai ka hiki o TMB neoantigens, no ka mea, ʻo ke kahua kikoʻī o ka hoʻololi ʻana he mea nui hoʻi; Hiki i nā hoʻololi ʻana i nā ala like ʻole o ka hōʻike antigen ke hoʻopili i ka hōʻike (a i ʻole ka hōʻike ʻole ʻana) o nā antigens hou i ka ʻōnaehana pale, e hōʻike ana i nā hiʻohiʻona intrinsic a me immunological pono e kūlike i mea e hana ai i nā pane ICI maikaʻi loa.

I kēia manawa, ana ʻia ʻo TMB ma o ka hoʻonohonoho ʻana o ka hanauna e hiki mai ana (NGS), hiki ke ʻokoʻa i waena o nā ʻoihana like ʻole (ma loko) a i ʻole nā ​​​​pahu kalepa i hoʻohana ʻia. Loaʻa i ka NGS ke kaʻina exome holoʻokoʻa (WES), ka hoʻonohonoho genome holoʻokoʻa, a me ka hoʻonohonoho ʻana i hoʻopaʻa ʻia, hiki ke loaʻa mai ka ʻiʻo tumo a me ka DNA tumor (ctDNA). He mea pono e hoʻomaopopo i nā ʻano ʻokoʻa like ʻole o ka maʻi maʻi he nui o ka TMB, me nā maʻi immunogenic e like me ka melanoma, NSCLC, a me ka squamous cell carcinoma loaʻa nā kiʻekiʻe TMB kiʻekiʻe. Pēlā nō, ʻokoʻa ka wehewehe ʻana o nā ʻano ʻike i hoʻolālā ʻia no nā ʻano tumo like ʻole o nā koina paepae TMB. Ma ke aʻo ʻana i ka NSCLC, melanoma, urothelial carcinoma, a me ka liʻiliʻi cell lung cancer, hoʻohana kēia mau ʻano ʻike i nā ʻano analytical like ʻole (e like me ka WES a i ʻole PCR ʻike no nā helu kikoʻī o nā genes pili) a me nā paepae (TMB kiʻekiʻe a i ʻole TMB haʻahaʻa).

ʻAʻole paʻa loa nā microsatellites. ʻO Microsatellite highly unstable (MSI-H), ma ke ʻano he biomarker pan cancer no ka pane ICI, he hana maikaʻi loa i ka wānana ʻana i ka pono o ka ICI i nā maʻi maʻi like ʻole. ʻO MSI-H ka hopena o nā hemahema hoʻoponopono mismatch (dMMR), e alakaʻi ana i ka helu mutation kiʻekiʻe, ʻoi aku hoʻi i nā wahi microsatellite, ka hopena i ka hana ʻana o ka nui o nā antigens hou a hoʻomaka i ka pane ʻana i ka clonal immune. Ma muli o ke kaumaha mutation kiʻekiʻe i hoʻokumu ʻia e dMMR, hiki ke noʻonoʻo ʻia nā maʻi maʻi MSI-H ma ke ʻano he ʻano o ka puʻuwai mutation kiʻekiʻe (TMB). Ma muli o nā hopena hoʻokolohua lapaʻau o KEYNOTE-164 a me KEYNOTE-158, ua ʻae ka FDA i ka pembrolizumab no ka mālama ʻana i nā maʻi maʻi MSI-H a i ʻole dMMR. ʻO kēia kekahi o nā lāʻau lapaʻau pan cancer mua i ʻae ʻia e ka FDA i alakaʻi ʻia e ka biology tumor ma mua o ka histology.

ʻOiai ke kūleʻa nui, aia kekahi mau pilikia e ʻike i ka wā e hoʻohana ai i ke kūlana MSI. No ka laʻana, hiki i ka 50% o nā maʻi maʻi maʻi maʻi colorectal dMMR ʻaʻohe pane i ka mālama ʻana i ka ICI, e hōʻike ana i ke koʻikoʻi o nā hiʻohiʻona ʻē aʻe i ka wānana pane. ʻO nā hiʻohiʻona koʻikoʻi ʻē aʻe o nā maʻi ʻaʻa ʻaʻole hiki ke loiloi ʻia e nā kahua ʻike i kēia manawa he mau kumu. No ka laʻana, ua loaʻa nā hōʻike i ka poʻe maʻi me ka hoʻololi ʻana i nā genes e hoʻopili ana i nā subunits catalytic koʻikoʻi o ka polymerase delta (POLD) a i ʻole polymerase ε (POLE) i loko o ka ʻāina DNA i nele i ka hilinaʻi replication a hōʻike i kahi phenotype "super mutation" i ko lākou mau maʻi koko. ʻO kekahi o kēia mau maʻi koko ua hoʻonui nui i ka microsatellite instability (no laila no MSI-H), akā ʻaʻole nele nā ​​protein hoʻoponopono mismatch (no laila ʻaʻole dMMR).

Eia kekahi, e like me TMB, pili pū ʻia ʻo MSI-H e nā ʻano antigen hou i hana ʻia e ka microsatellite instability, ka ʻike ʻana o ka host i nā ʻano antigen hou, a me ka pane ʻana o ka ʻōnaehana immune host. ʻOiai i loko o nā maʻi maʻi ʻano MSI-H, ua ʻike ʻia ka helu nui o nā hoʻololi nucleotide hoʻokahi ma ke ʻano he hoʻololi o nā kaʻa (nā hoʻololi ʻole o ka mea hoʻokele). No laila, ʻaʻole lawa ka hilinaʻi wale ʻana i ka nui o nā microsatellites i ʻike ʻia i loko o ka ʻōpū; ʻO ke ʻano maoli o ka hoʻololi ʻana (i ʻike ʻia ma o nā profile mutation kikoʻī) hiki ke hoʻomaikaʻi i ka hana wānana o kēia biomarker. Eia kekahi, ʻo kahi hapa liʻiliʻi wale nō o nā maʻi maʻi maʻi maʻi i nā maʻi maʻi MSI-H, e hōʻike ana i ka pono o kēia manawa no nā biomarkers pili ākea. No laila, ʻo ka ʻike ʻana i nā biomarkers pono ʻē aʻe e wānana i ka pono a alakaʻi i ka hoʻokele maʻi he wahi noiʻi koʻikoʻi.

ʻO ka noiʻi biomarker e pili ana i ka hui

Hāʻawi ʻia ke ʻano o ka hana a ICI e hoʻohuli i ka hoʻopau ʻana i ka cell immune ma mua o ke kuhikuhi pololei ʻana i nā ala intrinsic o nā cell tumor, pono e noiʻi hou aku i ka nānā ʻana i ka ʻōnaehana ulu ulu a me ka pilina ma waena o nā cell tumor a me nā cell immune, hiki ke kōkua i ka wehewehe ʻana i nā mea e pili ana i ka pane ICI. Nui nā pūʻulu noiʻi i aʻo i ka ʻōpū a i ʻole nā ​​hiʻohiʻona pale o nā ʻano kiko kikoʻī, e like me nā hiʻohiʻona ʻokoʻa a me nā hiʻohiʻona mutation gene immune, nā hemahema hōʻike antigen tumor, a i ʻole nā ​​kikowaena immune multicellular a i ʻole nā ​​hui (e like me nā hale lymphoid tertiary), hiki ke wānana i nā pane i ka immunotherapy.

Ua hoʻohana nā mea noiʻi i ka NGS e hoʻonohonoho i ka ʻōpū a me ka exome immune a me ka transcriptome o nā ʻiʻo maʻi ma mua a ma hope o ka mālama ʻana i ka ICI, a alakaʻi i ka nānā ʻana i nā kiʻi spatial. Ma ka hoʻohana ʻana i nā hiʻohiʻona i hoʻohui ʻia, i hui pū ʻia me nā ʻenehana e like me ka hoʻokaʻina ʻana o ke kelepona hoʻokahi a me ke kiʻi spatial, a i ʻole nā ​​hiʻohiʻona multi omics, ua hoʻomaikaʻi ʻia ka mana wānana o nā hopena lapaʻau ICI. Eia kekahi, ua hōʻike pū ʻia kahi ala holoʻokoʻa no ka loiloi ʻana i nā hōʻailona immune a me nā hiʻohiʻona intrinsic tumor. No ka laʻana, ʻoi aku ka maikaʻi o ke kaʻina hana hoʻonohonoho pūʻulu holoʻokoʻa e ana i ka manawa like i ka maʻi ʻaʻai a me nā ʻano immune ma mua o ka hoʻololi analytical hoʻokahi. Hōʻike kēia mau hopena i ka pono o ka hoʻohālikelike ʻana i ka maikaʻi o ka ICI ma kahi ʻano ākea, me ka hoʻohui ʻana i nā hopena loiloi o ka hiki ke pale aku i ka host, nā hiʻohiʻona intrinsic tumor, a me nā ʻāpana immune i loko o kēlā me kēia maʻi e wānana maikaʻi i nā mea maʻi e pane i ka immunotherapy.

Ma muli o ka paʻakikī o ka hoʻokomo ʻana i nā mea ʻokoʻa a me nā mea hoʻokipa i ka noiʻi biomarker, a me ka pono pono no ka hoʻohui lōʻihi o nā hiʻohiʻona microenvironment immune, ua hoʻomaka ka poʻe e ʻimi i nā biomarkers me ka hoʻohana ʻana i ka hoʻohālike kamepiula a me ke aʻo ʻana i ka mīkini. I kēia manawa, ua puka mai kekahi mau mea noiʻi hoʻokō honua i kēia kahua, e hōʻike ana i ka wā e hiki mai ana o ka oncology pilikino i kōkua ʻia e ka mīkini aʻo.

ʻO nā pilikia i kū ʻia e nā biomarkers pili i ke kino

Nā palena o nā ʻano analytical. Hana maikaʻi kekahi mau biomarkers koʻikoʻi i kekahi mau ʻano tumo, akā ʻaʻole pono i nā ʻano tumo ʻē aʻe. ʻOiai ʻoi aku ka ikaika o nā hiʻohiʻona ʻano kikoʻī ma mua o ka TMB a me nā mea ʻē aʻe, ʻaʻole hiki ke hoʻohana ʻia no ka ʻike ʻana i nā maʻi maʻi āpau. Ma kahi noiʻi e ʻimi ana i nā maʻi NSCLC, ua ʻike ʻia nā hiʻohiʻona mutation gene e ʻoi aku ka wānana o ka ICI efficacy ma mua o ka TMB kiʻekiʻe (≥ 10), akā ʻoi aku ka hapa o nā maʻi i hiki ʻole ke ʻike i nā hiʻohiʻona mutation gene.

ʻO ke ʻano like ʻole o ka tumo. ʻO ke ʻano biomarker e pili ana i ka ʻiʻo, he laʻana wale nō ma kahi kahua maʻi maʻi, ʻo ia hoʻi, ʻaʻole i hōʻike pololei ʻia ka loiloi o nā ʻāpana ʻokoʻa kikoʻī i ka hōʻike holoʻokoʻa o nā maʻi maʻi āpau i ka mea maʻi. No ka laʻana, ua ʻike nā haʻawina i ka heterogeneity i ka ʻōlelo PD-L1 ma waena a i loko o nā ʻōpū, a aia nā pilikia like me nā mea kikoʻī ʻē aʻe.

Ma muli o ka paʻakikī o nā ʻōnaehana olaola, nui paha nā mea biomarkers i hoʻohana mua ʻia. Eia kekahi, ʻo nā pūnaewele i loko o ka microenvironment tumo (TME) maʻamau maʻamau, no laila, ʻaʻole i hōʻike ʻia nā pilina i hōʻike ʻia i ka nānā ʻana i ka spatial i nā pilina maoli ma waena o nā pūnana tumo a me nā cell immune. ʻOiai inā hiki i nā biomarkers ke hōʻike kūpono i ke kaiapuni ʻokoʻa holoʻokoʻa i kahi manawa kikoʻī, hiki ke hoʻohuli ʻia kēia mau pahuhopu a hoʻololi ikaika i ka manawa, e hōʻike ana ʻaʻole i hōʻike maikaʻi ʻia kahi kiʻi paʻi i ka manawa.

ʻO ka maʻi heterogeneity. ʻOiai inā ʻike ʻia nā loli genetic e pili ana i ke kū'ē ICI, hiki i kekahi poʻe maʻi e lawe ana i nā biomarkers kū'ē i ʻike ʻia e pōmaikaʻi paha, ma muli paha o ka heterogeneity molecular a / a i ʻole ka pale ʻana i loko o ka ʻōpū a ma nā wahi ʻokoʻa. No ka laʻana, hiki i ka β 2-microglobulin (B2M) deficiency ke hōʻike i ke kūʻē hou a loaʻa paha i ka lāʻau lapaʻau, akā ma muli o ka heterogeneity o ka hemahema B2M ma waena o nā poʻe a i loko o nā ʻōpū, a me ka launa pū ʻana o nā mīkini hoʻololi ʻike immune i kēia mau maʻi, ʻaʻole hiki i ka hemahema B2M ke wānana ikaika i ke kūʻē ʻana i kēlā me kēia lāʻau. No laila, ʻoiai ka loaʻa ʻana o ka hemahema B2M, hiki i ka poʻe maʻi ke pōmaikaʻi mai ka ICI therapy.

Nā biomarkers longitudinal e pili ana i ka hui
Hiki ke loli ka ʻōlelo o nā biomarkers i ka manawa a me ka hopena o ka mālama ʻana. Hiki ke nānā ʻole ʻia kēia mau hoʻololi ʻana i nā loiloi static a hoʻokahi o nā ʻōpū a me ka immunobiology, a hiki ke nānā ʻia nā loli i ka TME tumor a me nā pae pane immune host. Ua hōʻike ʻia nā haʻawina he nui i ka loaʻa ʻana o nā laʻana ma mua a i ka wā o ka mālama ʻana hiki ke ʻike pololei i nā loli e pili ana i ka mālama ʻana i ka ICI. Hōʻike kēia i ke koʻikoʻi o ka loiloi biomarker dynamic.

Nā biomarkers pili koko
ʻO ka maikaʻi o ka nānā ʻana i ke koko aia i kona hiki ke loiloi biologically i nā ʻeha ʻeha o kēlā me kēia kanaka, e noʻonoʻo ana i ka heluhelu awelika ma mua o ka heluhelu ʻana i ka pūnaewele kikoʻī, kūpono loa ia no ka loiloi ʻana i nā loli ikaika e pili ana i ka mālama ʻana. Ua hōʻike ʻia nā hopena noiʻi he nui i ka hoʻohana ʻana i ka DNA tumor circulating (ctDNA) a i ʻole circulating tumor cells (CTC) e loiloi i ka liʻiliʻi o ke koena o ka maʻi (MRD) hiki ke alakaʻi i nā hoʻoholo lapaʻau, akā ua liʻiliʻi kēia mau hōʻike i ka wānana inā hiki i nā maʻi ke pōmaikaʻi mai nā immunotherapies e like me ICI. No laila, pono e hui pū ʻia ka hoʻāʻo ʻana o ctDNA me nā ʻano hana ʻē aʻe e ana i ka hoʻoulu ʻana i ka immune a i ʻole ka hoʻokipa ʻana i ka hiki ke pale aku. Ma keia manao, ua holomua i ka immunophenotyping o peripheral blood mononuclear cell (PBMCs) a me ka proteomic analysis of extracellular vesicles and plasma. No ka laʻana, ʻo nā ʻano subtypes immune cell peripheral (e like me CD8+T cell), hōʻike kiʻekiʻe o nā molekole helu hoʻopaʻa kino (e like me PD1 ma nā ʻāpana CD8+T peripheral), a me nā kiʻekiʻe kiʻekiʻe o nā protein like ʻole i loko o ka plasma (e like me CXCL8, CXCL10, IL-6, IL-10, PRAP1, a me VEGFA supplements) hiki ke lilo i mea hoʻohui biomark maikaʻi. ʻO ka pōmaikaʻi o kēia mau ʻano hou, ʻo ia ka hiki ke loiloi i nā loli i loko o ka ʻōpū (e like me nā loli i ʻike ʻia e ctDNA) a hiki ke hōʻike i nā loli i ka ʻōnaehana pale o ka mea maʻi.

Radiomics
Hiki i nā mea wānana o ka ʻikepili kiʻi ke hoʻokō pono i nā palena o ka biomarker sampling tissue a me ka biopsy, a hiki ke nānā i ka ʻōpū holoʻokoʻa a me nā pae metastatic ʻē aʻe i kēlā me kēia manawa. No laila, lilo paha lākou i ʻāpana koʻikoʻi o nā biomarkers dynamic non-invasive i ka wā e hiki mai ana. Hiki i nā radiomics Delta ke helu helu i nā loli i nā hiʻohiʻona ʻokoʻa he nui (e like me ka nui o ka tumo) i nā manawa like ʻole, e like me ka wā ma mua a ma hope o ka mālama ʻana i ka ICI, i ka wā o ka mālama ʻana, a me ka hahai ʻana ma hope. ʻAʻole hiki i ka Delta radiomics ke wānana wale i ka pane mua a i ʻole ka pane ʻana i ka mālama mua ʻana, akā ʻike pū kekahi i ke kūʻē ʻana i ka ICI i ka manawa maoli a nānā i ka hoʻi hou ʻana ma hope o ke kala piha ʻana. ʻOi aku ka maikaʻi o ke kumu hoʻohālike kiʻi i hoʻomohala ʻia ma o ka ʻenehana aʻo mīkini ma mua o ke kūlana RECIST kuʻuna i ka wānana i ka pane ʻana i ka lāʻau a me nā hanana pōʻino. Hōʻike ka noiʻi o kēia manawa he wahi ma lalo o ka pihi (AUC) kēia mau hiʻohiʻona radiomics a hiki i ka 0.8 a i ka 0.92 i ka wānana ʻana i ka pane ʻana o ka lāʻau lapaʻau.

ʻO kekahi pono o ka radiomics ʻo ia ka hiki ke ʻike pololei i ka holomua pseudo. Hiki i ke kŘkohu radiomics i kūkulu 'ia ma o ka mīkini a'o 'ana ke 'ike pono i waena o ka 'oia'i'o a me ka 'ole ka holomua 'ana ma ke ana 'ana i ka CT a i 'ole ka 'ikepili PET no kēlā me kēia ma'i koko, me nā mea e like me ke 'ano, ka ikaika, a me ke 'ano, me ka AUC o 0.79. Hiki ke hoʻohana ʻia kēia mau hiʻohiʻona radiomics i ka wā e hiki mai ana e pale i ka hoʻopau ʻana i ka lāʻau lapaʻau ma muli o ka manaʻo hewa ʻole o ka piʻi ʻana o ka maʻi.

ʻO microbiota ʻōpū
Manaʻo ʻia nā mea biomarkers o ka gut microbiota e wānana i ka pane therapeutic o ICI. Ua hōʻike ʻia nā noiʻi he nui e pili pono ana kahi microbiota puʻuwai kikoʻī i ka pane ʻana o nā ʻano maʻi maʻi like ʻole i ka mālama ʻana i ka ICI. No ka laʻana, i nā poʻe maʻi me ka melanoma a me ka maʻi maʻi ate, pili ka nui o ka bacteria Ruminococcaceae me ka pane immunotherapy PD-1. He mea maʻamau ka hoʻonui ʻana o Akkermansia muciniphila i nā poʻe maʻi me ka maʻi maʻi ate, ka maʻi ʻaʻai māmā, a i ʻole ka maʻi maʻi maʻi renal cell, e pane maikaʻi ana i ka mālama ʻana i ka ICI.

Eia kekahi, hiki ke kūʻokoʻa ka ʻōnaehana aʻo mīkini hou i nā ʻano tumo a hoʻopili i nā genera bacterial gut kikoʻī me ka pane therapeutic o immunotherapy. Ua hōʻike pū ʻia nā haʻawina ʻē aʻe i ke kuleana kikoʻī a kēlā me kēia pūʻulu bacteria e hoʻoponopono i ka ʻōnaehana immune host, e ʻimi hou aʻe i ka pale ʻana a i ʻole ka hoʻoikaika ʻana i ka pakele ʻana o nā cell cancer.

ʻO ka lāʻau neoadjuvant
Hiki ke alakaʻi i nā hoʻolālā lāʻau lapaʻau hope. Hiki i ka ho'āʻo hoʻokolohua neoadjuvant ke loiloi i ka hopena therapeutic ma o ke kala ʻana o ka pathological i nā specimens surgical. I ka mālama ʻana i ka maʻi melanoma, pili ka pane pathological mua (MPR) me ka hoʻihoʻi hou ʻana o ke ola manuahi. Ma ka hoʻokolokolo PRADO, hoʻoholo ka poʻe noiʻi i nā kaʻina hana lapaʻau e hiki mai ana, e like me ka ʻoki ʻana a/a i ʻole ka adjuvant therapy, e pili ana i ka ʻikepili kala ʻia pathological kikoʻī.

Ma waena o nā ʻano like ʻole o ka maʻi maʻi maʻi, ʻaʻohe mau koho adjuvant therapy hou i nele i ke poʻo i ke poʻo hoʻohālikelike. No laila, ʻo ka koho ma waena o ka immunotherapy monotherapy a i ʻole ka hui pū ʻana e hoʻoholo pū ʻia e ke kauka hele a me ka mea maʻi. I kēia manawa, ua hoʻomohala nā mea noiʻi i kahi hiʻohiʻona interferon gamma (IFN gamma) i loaʻa nā genes 10 ma ke ʻano he biomarker no ka wānana ʻana i ke kala ʻana o ka pathological i ka melanoma ma hope o ka neoadjuvant therapy. Hoʻohui hou lākou i kēia mau hiʻohiʻona i kahi algorithm e koho i nā maʻi me nā pane ikaika a nāwaliwali paha i ka neoadjuvant therapy. Ma kahi haʻawina hahai i kapa ʻia ʻo DONIMI, ua hoʻohana nā mea noiʻi i kēia helu, i hui pū ʻia me ka loiloi paʻakikī, ʻaʻole wale no ka wānana i ka pane ʻana i ka lāʻau, akā no ka hoʻoholo ʻana i ka pae III melanoma maʻi e koi ai i ka hoʻohui ʻana o ka histone deacetylase inhibitors (HDACi) e hoʻomaikaʻi i ka pane i ka neoadjuvant ICI lapaʻau.

ʻO ke kumu hoʻohālike i loaʻa mai i nā maʻi
Hiki i nā kumu hoʻohālike in vitro ke wānana i nā pane kikoʻī o ka maʻi. ʻAʻole like me ka platform in vitro i hoʻohana ʻia no ka nānā ʻana i ka spectrum pane ʻana i ka lāʻau o nā hematologic malignancies, ʻoi aku ka paʻakikī o nā maʻi maʻi ma muli o kā lākou microstructure tumor kūʻokoʻa a me nā pilina immune immune. ʻAʻole hiki ke maʻalahi ka moʻomeheu cell tumor maʻalahi i kēia mau hiʻohiʻona paʻakikī. I kēia hihia, hiki i ka maʻi e like me nā ʻāpana a i ʻole nā ​​ʻāpana o nā mea maʻi ke hoʻopaʻi no kēia mau palena o ke kūkulu ʻana, no ka mea hiki iā lākou ke mālama i ke ʻano o ka cell tumo mua a hoʻohālikelike i nā pilina me nā lymphoid a me nā myeloid immune cell e loiloi i nā pane ICI ma ke ʻano kikoʻī maʻi.

Ua hoʻohana kekahi mau haʻawina holomua ma Kina a me ʻAmelika Hui Pū ʻIa i kēia hiʻohiʻona kiʻekiʻe ʻekolu-dimensional in vitro tumor. Hōʻike nā hopena i hiki i kēia mau hiʻohiʻona ke wānana maikaʻi i ka pane ʻana o ka maʻi maʻi ʻāʻī, ka maʻi ʻaʻai colon, ka maʻi maʻi umauma, ka melanoma a me nā maʻi maʻi ʻē aʻe i ICI. Hoʻokumu kēia i ke kumu no ka hōʻoia hou ʻana a me ka hoʻohālikelike ʻana i ka hana wānana o kēia mau hiʻohiʻona.