Niaj hnub no, immunotherapy tau txhim kho cov txiaj ntsig kev kho mob hauv ntau tus neeg mob qog noj ntshav, suav nrog melanoma, thiab lwm yam, Tab sis cov kev kho mob no tsuas yog siv tau rau cov neeg mob xwb, Ntau cov kev tshawb fawb tab tom saib yuav ua li cas txhim kho tus neeg mob lub cev teb, suav nrog kev tsom mus rau. Yuav ua li cas txhim kho qog-infiltrating lymphocytes (TILs, Kev Ua Haujlwm ntawm cov qauv-infiltrating lymphocytes), TILs yog cov tshuaj tiv thaiv kab mob tshwj xeeb hauv cov qog, uas tuaj yeem lees paub thiab tua cov qog nqaij hlav cancer, tab sis feem ntau tsis muaj TILs txaus, lossis tsis txaus. los siv cov lus teb muaj zog rau kev pheej hmoo inhibit qog loj hlob thiab kis tau.
Tsis ntev los no, luam tawm nyob rau hauv ib txoj kev tshawb no nyob rau hauv lub thoob ntiaj teb phau ntawv journal Nature Cancer txoj cai "Fucosylation ntawm HLA-DRB1 tswj CD4 ntxiv rau T cell-mediated anti-melanoma tiv thaiv kab mob thiab txhim kho kev tiv thaiv kab mob", Cov kws tshawb fawb los ntawm Mofitt Cancer Research Medium Institute tau txheeb xyuas txoj hauv kev zoo. kom nce tus naj npawb ntawm TILs thiab antitumour kev ua ub no, nyob rau hauv tsab xov xwm, Tus neeg tshawb xyuas tau hais tias, Ib qho khoom noj tsis muaj tshuaj lom neeg noj qab haus huv, L-trehalose (L-fucose), nrog cov qib siab dua hauv cov xim liab thiab xim av seaweed, lossis ib qho uas tuaj yeem nce ntxiv. cov qib ntawm TILs thiab txhawb lub cev tiv thaiv qog noj ntshav, Nws kuj tseem txhim kho cov kev kho mob ntawm immunotherapy. Txawm hais tias L-trehalose muaj nyob hauv ntau cov khoom noj, nws tuaj yeem ua ke los ntawm cov hlwb hauv lub cev los ntawm kev decomposition thiab hloov lwm cov molecules. Nws yog ib qho tseem ceeb heev rau kev tiv thaiv thiab kev loj hlob ntawm lub cev. Kev sib txuam tsis zoo thiab kev siv L-trehalose feem ntau cuam tshuam nrog kev tshwm sim ntawm ntau yam kab mob, suav nrog mob qog noj ntshav.
Cov kws tshawb fawb Lau tau hais tias, L-tag nrho cov theem ntawm trehalose hauv melanoma, thiab nyob rau hauv cov txheej txheem ntawm cov kab mob kev loj hlob hlwb siv L-trehalose yuav hloov, txawm li cas los xij, peb pom tias los ntawm kev noj zaub mov kom nce qib ntawm L-trehalose yuav inhibit qog, thiab nce qib ntawm TILs, tab sis kuj tuaj yeem txhim kho kev ua tau zoo ntawm qee qhov kev tiv thaiv kab mob hauv cov qauv tsiaj, hauv tib neeg lub cev, melanoma nyob rau theem siab ntawm L-trehalose lossis cuam tshuam nrog cov kab mob tsawg dua thiab cov neeg mob muaj cov lus teb zoo dua rau kev kho. Cov neeg tshawb xyuas xav txiav txim siab txog cov txheej txheem molecular tom qab qhov nce ntawm TILs thiab induction ntawm antitumor kev ua haujlwm ntawm lub cev, Hauv 7 xyoo dhau los, Lawv tau ua ntau yam kev sim thiab thawj zaug, L-trehalose tswj kev cuam tshuam ntawm CD4 ntxiv. T hlwb (chav kawm I TIL) thiab melanoma hlwb; Hauv kev sim nas, Cov neeg tshawb nrhiav pom tias, nce qib L-trehalose hauv cov qog hlwb los ntawm kev tswj hwm qhov ncauj ntawm L-trehalose, Txo cov qog loj hlob thiab nce tag nrho cov qib ntawm TILs, Ntawm ntau hom kab mob tiv thaiv kab mob uas ua rau TILs. , CD4 ntxiv rau T hlwb ua lub luag haujlwm tseem ceeb hauv kev kho cov theem ntawm TILs thiab yog li hauv kev txo qis melanoma thaum L-trehalose kho, Yog li cov kws tshawb fawb tau txheeb xyuas qhov tseem ceeb ntawm cov txheej txheem molecular, uas tuaj yeem txhawb nqa L-trehalose-mediated antitumor kev ua ntawm CD4 ntxiv rau T. hlwb.
Thaum tib neeg xav txog qab zib, lawv feem ntau xav txog qabzib lossis sucrose, uas yog cov suab thaj uas siv los ntawm lub cev kom tau txais lub zog. Tsis zoo li cov suab thaj no, L-trehalose tsis yog siv los ntawm cov hlwb kom tau txais lub zog, tab sis los kho cov protein kom zoo kho lawv tus cwj pwm thiab kev ua ub no; Cov kws tshawb fawb pom tias ntxiv L-trehalose rau HLA-DRB 1 cov protein txhawb nqa nws qhov chaw nyob rau saum npoo ntawm cov hlwb melanoma, yog li ua rau cov qog nqaij hlav tiv thaiv kab mob hauv cell mediated los ntawm CD4 ntxiv rau T hlwb. Ntxiv nrog rau kev kho kom zoo nkauj cov protein nyob rau hauv cov qog hlwb, cov kws tshawb fawb kuj pom tias L-trehalose tuaj yeem hloov pauv biology ntawm CD4 ntxiv rau T hlwb thiab lwm lub cev tiv thaiv kab mob thiab kev coj cwj pwm, thiab nws zoo li siv los tswj hwm lub cev tiv thaiv kab mob, cov no. Cov kev tshawb fawb pom tias kev siv L-trehalose los txhim kho kev kho mob qog noj ntshav rau cov neeg mob qog noj ntshav yog qhov tseem ceeb heev, yog li ntawd, tom qab cov kws tshawb fawb tau tshawb fawb ntxiv tias qhov ncauj L-trehalose tuaj yeem txhim kho cov tshuaj tiv thaiv kab mob hauv kev kho mob ntawm cov nyhuv curative ntawm ib feem ntawm melanoma qauv.
Tom ntej no, cov kws tshawb fawb tau saib cov qog nqaij hlav los ntawm peb lub chaw mob qog noj ntshav, txhawm rau txheeb xyuas seb qib L-trehalose thiab HLA-DRB 1 cov protein cuam tshuam cov lus teb rau cov tshuaj tiv thaiv PD-1, thiab pom tias cov neeg mob uas teb rau PD. -1 txoj kev kho tau muaj cov qib siab ntawm L-trehalose thiab L-trehalose-decorated HLA-DRB 1, qhia tias nws yuav raug siv los ua biomarker muaj peev xwm los pab kwv yees cov lus teb rau kev tiv thaiv kab mob. Peb txoj kev tshawb fawb txheeb xyuas cov txheej txheem molecular tom qab L-trehalose tswj qhov cuam tshuam tseem ceeb ntawm melanoma thiab lub cev tiv thaiv kab mob, uas tuaj yeem siv rau kev kho mob los ntawm tsuas yog muab L-trehalose, thiab tseem tuaj yeem pab cov kws tshawb fawb siv qab zib los tiv thaiv qog noj ntshav yav tom ntej, kws tshawb fawb Lau hais.
Cov kws tshawb fawb tom qab cia siab tias yuav txhais lawv cov kev tshawb pom hauv preclinical rau hauv kev pab ncaj qha rau cov neeg mob thiab txiav txim siab ntau npaum li cas L-trehalose tuaj yeem txhim kho kev siv tshuaj tiv thaiv kab mob, tau kawg kev sim tshuaj me me hauv cov neeg mob melanoma; Hauv kev xaus, qhov kev tshawb pom qhia tias fucosylation (fucosylation) yuav yog tus neeg nruab nrab tseem ceeb ntawm kev tiv thaiv kab mob tiv thaiv kab mob, txoj kev tshawb no kuj qhia tau tias L-trehalose yog ib qho muaj zog tiv thaiv kom muaj kev nyab xeeb nce qib ntawm TILs thiab kho cov txiaj ntsig hauv melanoma.
