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LaFleur, Martin

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LaFleur

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LaFleur, Martin

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20171

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Author's Publications: search.filters.isAuthorOfPublication.254209a7-5c8c-4dae-b6a9-45fdead1513e

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    Neuropeptide signaling orchestrates T cell differentiation
    Hou, Yu; Sun, Lin-Yu; LaFleur, Martin; Huang, Linglin; Lambden, Conner; Thakore, Pratiksha; Geiger-Schuller, Kathryn; Kimura, Kimitoshi; Tang, Ruihan; Shi, Jingwen; Deng, Liwen; Subramanian, Ayshwarya; Wallrapp, Antonia; Choi, Hee Sun; Kye1, Yoon-Chul; Ashenberg, Orr; Schiebinger, Geoffrey; Doench, John; Chiu, Isaac; Regev, Aviv; Sharpe, Arlene; Kuchroo, Vijay
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    PD-L1 on tumor cells is sufficient for immune evasion in immunogenic tumors and inhibits CD8 T cell cytotoxicity
    (The Rockefeller University Press, 2017) Juneja, Vikram R.; McGuire, Kathleen A.; Manguso, Robert T.; LaFleur, Martin; Collins, Natalie; Haining, W. Nicholas; Freeman, Gordon J.; Sharpe, Arlene
    It is unclear whether PD-L1 on tumor cells is sufficient for tumor immune evasion or simply correlates with an inflamed tumor microenvironment. We used three mouse tumor models sensitive to PD-1 blockade to evaluate the significance of PD-L1 on tumor versus nontumor cells. PD-L1 on nontumor cells is critical for inhibiting antitumor immunity in B16 melanoma and a genetically engineered melanoma. In contrast, PD-L1 on MC38 colorectal adenocarcinoma cells is sufficient to suppress antitumor immunity, as deletion of PD-L1 on highly immunogenic MC38 tumor cells allows effective antitumor immunity. MC38-derived PD-L1 potently inhibited CD8+ T cell cytotoxicity. Wild-type MC38 cells outcompeted PD-L1–deleted MC38 cells in vivo, demonstrating tumor PD-L1 confers a selective advantage. Thus, both tumor- and host-derived PD-L1 can play critical roles in immunosuppression. Differences in tumor immunogenicity appear to underlie their relative importance. Our findings establish reduced cytotoxicity as a key mechanism by which tumor PD-L1 suppresses antitumor immunity and demonstrate that tumor PD-L1 is not just a marker of suppressed antitumor immunity.