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Collins, Natalie

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Collins

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Natalie

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Collins, Natalie
Author's Publications: search.filters.isAuthorOfPublication.eb177c3c-c526-49d2-8f78-56fa96378b70

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    A single-cell and single-nucleus RNA-Seq toolbox for fresh and frozen human tumors
    (Springer Science and Business Media LLC, 2020-05-01) Slyper, Michal; Porter, Caroline; Ashenberg, Orr; Waldman, Julia; Drokhlyansky, Eugene; Wakiro, Isaac; Smilie, Christopher; Smith-Rosario, Gabriela; Wu, Jingyi; Dionne, Danielle; Vigneau, Sebastien; Jane-Valbuena, Judit; Tickle, Timothy; Napolitano, Sara; Su, Mei-Ju; Patel, Anand; Karlstrom, Asa; Gristch, Simon; Nomura, Masashi; Waghray, Avinash; Gohil, Satyen; Tsankov, Alexander; Jerby-Arnon, Livnat; Cohen, Ofir; Klughammer, Johanna; Rosen, Yanay; Gould, Joshua; Nguyen, Lan; Hofree, Matan; Tramontozzi, Peter; Levy, Rachel; Li, Bo; Wu, Catherine; Izar, Benjamin; Haq, Rizwan; Hodi, Stephen; Yoon, Charles; Hata, Aaron; Baker, Suzanne; Suva, Mario; Bueno, Raphael; Stover, Elizabeth; Clay, Michael; Dyer, M Aiven; Collins, Natalie; Matulonis, Ursula; Wagle, Nikhil; Johnson, Bruce; Rotem, Asaf; Rozenblatt-Rosen, Orit; Regev, Aviv
    Single-cell genomics is essential to chart tumor ecosystems. Although single-cell RNA-Seq (scRNA-Seq) profiles RNA from cells dissociated from fresh tumors, single-nucleus RNA-Seq (snRNA-Seq) is needed to profile frozen or hard-to-dissociate tumors. Each requires customization to different tissue and tumor types, posing a barrier to adoption. Here, we have developed a systematic toolbox for profiling fresh and frozen clinical tumor samples using scRNA-Seq and snRNA-Seq, respectively. We analyzed 216,490 cells and nuclei from 40 samples across 23 specimens spanning eight tumor types of varying tissue and sample characteristics. We evaluated protocols by cell and nucleus quality, recovery rate and cellular composition. scRNA-Seq and snRNA-Seq from matched samples recovered the same cell types, but at different proportions. Our work provides guidance for studies in a broad range of tumors, including criteria for testing and selecting methods from the toolbox for other tumors, thus paving the way for charting tumor atlases.
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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.