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From the Current Issue

  • Research Articles | AuthorChoice
    St. Jude Cloud: A Pediatric Cancer Genomic Data-Sharing Ecosystem
    Clay McLeod, Alexander M. Gout, Xin Zhou, Andrew Thrasher, Delaram Rahbarinia, Samuel W. Brady, Michael Macias, Kirby Birch, David Finkelstein, Jobin Sunny, Rahul Mudunuri, Brent A. Orr, Madison Treadway, Bob Davidson, Tracy K. Ard, Arthur Chiao, Andrew Swistak, Stephanie Wiggins, Scott Foy, Jian Wang, Edgar Sioson, Shuoguo Wang, J. Robert Michael, Yu Liu, Xiaotu Ma, Aman Patel, Michael N. Edmonson, Mark R. Wilkinson, Andrew M. Frantz, Ti-Cheng Chang, Liqing Tian, Shaohua Lei, S.M. Ashiqul Islam, Christopher Meyer, Naina Thangaraj, Pamella Tater, Vijay Kandali, Singer Ma, Tuan Nguyen, Omar Serang, Irina McGuire, Nedra Robison, Darrell Gentry, Xing Tang, Lance E. Palmer, Gang Wu, Ed Suh, Leigh Tanner, James McMurry, Matthew Lear, Alberto S. Pappo, Zhaoming Wang, Carmen L. Wilson, Yong Cheng, Soheil Meshinchi, Ludmil B. Alexandrov, Mitchell J. Weiss, Gregory T. Armstrong, Leslie L. Robison, Yutaka Yasui, Kim E. Nichols, David W. Ellison, Chaitanya Bangur, Charles G. Mullighan, Suzanne J. Baker, Michael A. Dyer, Geralyn Miller, Scott Newman, Michael Rusch, Richard Daly, Keith Perry, James R. Downing and Jinghui Zhang
    Cancer Discov May 1 2021 11 (5) 1082-1099; DOI:10.1158/2159-8290.CD-20-1230

    The St. Jude Cloud enables sharing, visualization, and analysis of large datasets on pediatric cancer and other catastrophic childhood illnesses; recent use cases include classification of and investigations of mutation rates in pediatric cancers.

  • Research Articles | AuthorChoice
    Metastasis and Immune Evasion from Extracellular cGAMP Hydrolysis
    Jun Li, Mercedes A. Duran, Ninjit Dhanota, Walid K. Chatila, Sarah E. Bettigole, John Kwon, Roshan K. Sriram, Matthew P. Humphries, Manuel Salto-Tellez, Jacqueline A. James, Matthew G. Hanna, Johannes C. Melms, Sreeram Vallabhaneni, Kevin Litchfield, Ieva Usaite, Dhruva Biswas, Rohan Bareja, Hao Wei Li, Maria Laura Martin, Princesca Dorsaint, Julie-Ann Cavallo, Peng Li, Chantal Pauli, Lee Gottesdiener, Benjamin J. DiPardo, Travis J. Hollmann, Taha Merghoub, Hannah Y. Wen, Jorge S. Reis-Filho, Nadeem Riaz, Shin-San Michael Su, Anusha Kalbasi, Neil Vasan, Simon N. Powell, Jedd D. Wolchok, Olivier Elemento, Charles Swanton, Alexander N. Shoushtari, Eileen E. Parkes, Benjamin Izar and Samuel F. Bakhoum
    Cancer Discov May 1 2021 11 (5) 1212-1227; DOI:10.1158/2159-8290.CD-20-0387

    When expressed by cancer cells, the transmembrane glycoprotein ENPP1 hydrolyzed cGAS-generated extracellular cGAMP—which would otherwise elicit a STING-mediated antitumor response—to produce AMP that was processed into immunosuppressive adenosine.

  • Research Articles | AuthorChoice
    Design and Efficacy of a Monovalent Bispecific PD-1/CTLA4 Antibody That Enhances CTLA4 Blockade on PD-1+ Activated T Cells
    Simon J. Dovedi, Matthew J. Elder, Chunning Yang, Suzanne I. Sitnikova, Lorraine Irving, Anna Hansen, James Hair, Des C. Jones, Sumati Hasani, Bo Wang, Seock-Ah Im, Ben Tran, Deepa S. Subramaniam, Shelby D. Gainer, Kapil Vashisht, Arthur Lewis, Xiaofang Jin, Stacy Kentner, Kathy Mulgrew, Yaya Wang, Michael G. Overstreet, James Dodgson, Yanli Wu, Asis Palazon, Michelle Morrow, Godfrey J. Rainey, Gareth J. Browne, Frances Neal, Thomas V. Murray, Aleksandra D. Toloczko, William Dall'Acqua, Ikbel Achour, Daniel J. Freeman, Robert W. Wilkinson and Yariv Mazor
    Cancer Discov May 1 2021 11 (5) 1100-1117; DOI:10.1158/2159-8290.CD-20-1445

    Combined blockade of CTLA4 and the PD-1–PD-L1 axis can be effective but is limited by immune-related adverse events, prompting the development of a bispecific antibody (MEDI5752) targeting PD-1 and CTLA4; this treatment limited tumor growth in vivo.

  • Research Articles
    Gut Microbiome Directs Hepatocytes to Recruit MDSCs and Promote Cholangiocarcinoma
    Qianfei Zhang, Chi Ma, Yi Duan, Bernd Heinrich, Umberto Rosato, Laurence P. Diggs, Lichun Ma, Soumen Roy, Qiong Fu, Zachary J. Brown, Simon Wabitsch, Vishal Thovarai, Jianyang Fu, Dechun Feng, Benjamin Ruf, Linda L. Cui, Varun Subramanyam, Karen M. Frank, Sophie Wang, David E. Kleiner, Thomas Ritz, Christian Rupp, Bin Gao, Thomas Longerich, Alexander Kroemer, Xin Wei Wang, Mathuros Ruchirawat, Firouzeh Korangy, Bernd Schnabl, Giorgio Trinchieri and Tim F. Greten
    Cancer Discov May 1 2021 11 (5) 1248-1267; DOI:10.1158/2159-8290.CD-20-0304

    In mice with impaired gut barrier function, liver exposure to Gram-negative commensal bacteria led to TLR4-dependent recruitment of immunosuppressive myeloid-derived suppressor cells, which promoted cholangiocarcinoma.

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