文章基本信息

标题：PD-L1 Expression Affects Neoantigen Presentation
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作者：Masahiro Okada ; Kanako Shimizu ; Tomonori Iyoda 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：6
页码：1-41
DOI：10.1016/j.isci.2020.101238
语种：English
出版社：Elsevier
摘要：SummaryAlthough PD-L1 expression on tumor is related to the prognosis of immune checkpoint blockade (ICB) therapy, a recent study also demonstrated clinical benefits even in patients without PD-L1 expression. To understand the relationship between innate resistance and antitumor cytotoxic T lymphocyte (CTL) responses especially against neoantigens, the interaction between PD-L1+or genetically PD-L1-deleted colorectal tumors and CTLs was assessed under an ICB therapy, finding the robust CTL activation in PD-L1-deleted tumor-bearing mice. Using antigen libraries based on immunogenomics, we identified three H2-Kb-restricted, somatic-mutated immunogenic neoantigens by utilizing enhanced CTLs responses due to PD-L1 deficiency. Furthermore, we identified three T cell receptor (TCR) repertoires relevant to the neoantigens, confirming the response of TCR-gene-transduced CTLs to parental tumor cells. Notably, neoantigen-pulsed dendritic cell (DC) therapy reversed the tumor tolerance. Thus, innate resistance of tumors determines their responsiveness to neoantigens and mixed neoantigen peptides may be useful in DC therapy against innate resistance type tumor.Graphical AbstractDisplay OmittedHighlights•Poor prognosis of PD-L1-expressing tumors in some cancers•Identification of TCRVα and Vβ repertoire responsive for H2-Kb-restricted neoantigens•Neoantigen-epitope-pulsed DC therapy demonstrates antitumor effect in vaccineBiological Sciences; Immunology; Cancer