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Stover, Elizabeth

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Stover

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Elizabeth

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Stover, Elizabeth

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2015 - 20202

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Author's Publications: search.filters.isAuthorOfPublication.6e401b92-eebb-4726-a8ca-0e658cc8d675

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    Association of Polymerase e–Mutated and Microsatellite-Instable Endometrial Cancers With Neoantigen Load, Number of Tumor-Infiltrating Lymphocytes, and Expression of PD-1 and PD-L1
    (American Medical Association (AMA), 2015) Howitt, Brooke E.; Shukla, Sachet; Sholl, Lynette; Ritterhouse, Lauren L.; Watkins, Jaclyn Christine; Rodig, Scott; Stover, Elizabeth; Strickland, Kyle C.; D'Andrea, Alan; Wu, Catherine; Matulonis, Ursula; Konstantinopoulos, Panagiotis
    Importance Immune checkpoint inhibitor therapy has shown benefit in various cancers, but their potential in endometrial cancer (EC) is unknown. Observations Prediction of neoantigen load was performed using sequencing data from the Cancer Genome Atlas data set. Evaluation of tumor-infiltrating lymphocytes (TILs) and PD-1 and PD-L1 expression was performed in 63 patients with EC referred to our institution. The predicted median (range) neoantigen load (predicted neoepitopes per sample) was proportional to the mutational load: highest in ultramutated polymerase e (POLE) tumors (8342 [628-20 440]), less in hypermutated MSI (541 [146-8063]; P < .001), and lowest in microsatellite-stable tumors (70.5 [7-1877]; P < .001). The POLE and MSI ECs exhibited higher numbers of CD3+ (44.5 vs 21.8; P = .001) and CD8+ (32.8 vs 13.5; P < .001) TILs compared with microsatellite-stable tumors. PD-1 was overexpressed in TILs (81% vs 28%; P < .001) and peritumoral lymphocytes (90% vs 28%; P < .001) of POLE and MSI tumors. PD-L1 expression was infrequently noted in tumor cells but was common in intraepithelial immune cells and more frequent in POLE and MSI tumors (39% vs 13%; P = .02). Conclusions and Relevance Polymerase e–mutated and MSI ECs are associated with high neoantigen loads and number of TILs, which is counterbalanced by overexpression of PD-1 and PD-L1. Polymerase e–mutated and MSI EC tumors may be excellent candidates for PD-1–targeted immunotherapies.
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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.