PMC:6562565 / 62071-63243 JSONTXT

{"project":"MyTest","denotations":[{"id":"31244820-25672397-35366359","span":{"begin":75,"end":78},"obj":"25672397"},{"id":"31244820-23983257-35366360","span":{"begin":202,"end":205},"obj":"23983257"},{"id":"31244820-27622077-35366361","span":{"begin":207,"end":210},"obj":"27622077"},{"id":"31244820-23983257-35366362","span":{"begin":299,"end":302},"obj":"23983257"},{"id":"31244820-27622077-35366363","span":{"begin":304,"end":307},"obj":"27622077"},{"id":"31244820-23983257-35366364","span":{"begin":331,"end":334},"obj":"23983257"},{"id":"31244820-30012853-35366365","span":{"begin":900,"end":902},"obj":"30012853"},{"id":"31244820-30012853-35366366","span":{"begin":1168,"end":1170},"obj":"30012853"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"text":"It has been demonstrated that CD73+ tumor cells are resistant to PD-1 ICB (401) and that simultaneous mAb-mediated blockade of CD73 and PD-1 synergistically enhances tumor control and survival in mice (382, 385). Mechanistically, the dual therapy augments intra-tumoral CD8+ tumor-specific T cells (382, 385) and IFNγ mRNA levels (382) as compared to single-agent treatments. Several clinical trials assessing anti-CD73 mAb treatment along with anti-PD-1 mAb (NCT03454451, NCT03549000) or anti-PDL-1 mAb (NCT02503774, NCT03773666, NCT03267589, NCT03334617) of advanced solid tumors are recruiting or underway. Intra-tumoral upregulation of CD38 and subsequent adenosine production was recently identified as a mechanism of acquired resistance to PD-1/PD-L1 blockade and mAb-mediated or pharmacologic inhibition of CD38 was shown to significantly improve the anti-tumor efficacy of an anti-PDL-1 mAb (96). In terms of mechanisms, tumors from mice receiving the combinatorial therapy displayed higher accumulation of CD8+ T cells, effector memory CD8+ T cells, ICOS+ CD4+ T cells and lower levels of MDSCs and Tregs as compared to tumors from single-agent treated mice (96)."}

{"project":"TEST0","denotations":[{"id":"31244820-75-82-3850507","span":{"begin":75,"end":78},"obj":"[\"25672397\"]"},{"id":"31244820-202-209-3850508","span":{"begin":202,"end":205},"obj":"[\"23983257\"]"},{"id":"31244820-207-214-3850509","span":{"begin":207,"end":210},"obj":"[\"27622077\"]"},{"id":"31244820-86-93-3850510","span":{"begin":299,"end":302},"obj":"[\"23983257\"]"},{"id":"31244820-91-98-3850511","span":{"begin":304,"end":307},"obj":"[\"27622077\"]"},{"id":"31244820-118-125-3850512","span":{"begin":331,"end":334},"obj":"[\"23983257\"]"},{"id":"31244820-230-236-3850513","span":{"begin":900,"end":902},"obj":"[\"30012853\"]"},{"id":"31244820-232-238-3850514","span":{"begin":1168,"end":1170},"obj":"[\"30012853\"]"}],"text":"It has been demonstrated that CD73+ tumor cells are resistant to PD-1 ICB (401) and that simultaneous mAb-mediated blockade of CD73 and PD-1 synergistically enhances tumor control and survival in mice (382, 385). Mechanistically, the dual therapy augments intra-tumoral CD8+ tumor-specific T cells (382, 385) and IFNγ mRNA levels (382) as compared to single-agent treatments. Several clinical trials assessing anti-CD73 mAb treatment along with anti-PD-1 mAb (NCT03454451, NCT03549000) or anti-PDL-1 mAb (NCT02503774, NCT03773666, NCT03267589, NCT03334617) of advanced solid tumors are recruiting or underway. Intra-tumoral upregulation of CD38 and subsequent adenosine production was recently identified as a mechanism of acquired resistance to PD-1/PD-L1 blockade and mAb-mediated or pharmacologic inhibition of CD38 was shown to significantly improve the anti-tumor efficacy of an anti-PDL-1 mAb (96). In terms of mechanisms, tumors from mice receiving the combinatorial therapy displayed higher accumulation of CD8+ T cells, effector memory CD8+ T cells, ICOS+ CD4+ T cells and lower levels of MDSCs and Tregs as compared to tumors from single-agent treated mice (96)."}

{"project":"2_test","denotations":[{"id":"31244820-25672397-35366359","span":{"begin":75,"end":78},"obj":"25672397"},{"id":"31244820-23983257-35366360","span":{"begin":202,"end":205},"obj":"23983257"},{"id":"31244820-27622077-35366361","span":{"begin":207,"end":210},"obj":"27622077"},{"id":"31244820-23983257-35366362","span":{"begin":299,"end":302},"obj":"23983257"},{"id":"31244820-27622077-35366363","span":{"begin":304,"end":307},"obj":"27622077"},{"id":"31244820-23983257-35366364","span":{"begin":331,"end":334},"obj":"23983257"},{"id":"31244820-30012853-35366365","span":{"begin":900,"end":902},"obj":"30012853"},{"id":"31244820-30012853-35366366","span":{"begin":1168,"end":1170},"obj":"30012853"}],"text":"It has been demonstrated that CD73+ tumor cells are resistant to PD-1 ICB (401) and that simultaneous mAb-mediated blockade of CD73 and PD-1 synergistically enhances tumor control and survival in mice (382, 385). Mechanistically, the dual therapy augments intra-tumoral CD8+ tumor-specific T cells (382, 385) and IFNγ mRNA levels (382) as compared to single-agent treatments. Several clinical trials assessing anti-CD73 mAb treatment along with anti-PD-1 mAb (NCT03454451, NCT03549000) or anti-PDL-1 mAb (NCT02503774, NCT03773666, NCT03267589, NCT03334617) of advanced solid tumors are recruiting or underway. Intra-tumoral upregulation of CD38 and subsequent adenosine production was recently identified as a mechanism of acquired resistance to PD-1/PD-L1 blockade and mAb-mediated or pharmacologic inhibition of CD38 was shown to significantly improve the anti-tumor efficacy of an anti-PDL-1 mAb (96). In terms of mechanisms, tumors from mice receiving the combinatorial therapy displayed higher accumulation of CD8+ T cells, effector memory CD8+ T cells, ICOS+ CD4+ T cells and lower levels of MDSCs and Tregs as compared to tumors from single-agent treated mice (96)."}