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From the Current Issue

  • Research Articles | AuthorChoice
    Modified Hypoxia-Inducible Factor Expression in CD8+ T Cells Increases Antitumor Efficacy
    Pedro Veliça, Pedro P. Cunha, Nikola Vojnovic, Iosifina Petrina Foskolou, David Bargiela, Milos Gojkovic, Helene Rundqvist and Randall S. Johnson
    Cancer Immunol Res April 1 2021 9 (4) 401-414; DOI:10.1158/2326-6066.CIR-20-0561

    In this study, ectopic expression of FIH-insensitive HIF2α enhances human CD8+ T-cell cytolytic function in vitro and in a xenograft model. Modifying HIF expression may provide a way to enhance the antitumor efficacy of adoptive T-cell therapy.

  • Research Articles
    Targeting PIM1-Mediated Metabolism in Myeloid Suppressor Cells to Treat Cancer
    Gang Xin, Yao Chen, Paytsar Topchyan, Moujtaba Y. Kasmani, Robert Burns, Peter J. Volberding, Xiaopeng Wu, Alexandra Cohn, Yiliang Chen, Chien-Wei Lin, Ping-Chih Ho, Roy Silverstein, Michael B. Dwinell and Weiguo Cui
    Cancer Immunol Res April 1 2021 9 (4) 454-469; DOI:10.1158/2326-6066.CIR-20-0433

    Myeloid-derived suppressor cells (MDSC) are a barrier to successful anti–PD-L1 therapy. The authors show that PIM1 facilitates CD36-mediated fatty acid uptake via the PPARγ pathway, promoting MDSC immunosuppressive activity, and that PIM1 inhibition overcomes resistance to anti–PD-L1 therapy.

  • Research Articles
    Modifications to the Framework Regions Eliminate Chimeric Antigen Receptor Tonic Signaling
    Elisa Landoni, Giovanni Fucá, Jian Wang, Venkat R. Chirasani, Zhiyuan Yao, Elena Dukhovlinova, Soldano Ferrone, Barbara Savoldo, Lee K. Hong, Peishun Shou, Silvia Musio, Francesco Padelli, Gaetano Finocchiaro, Miriam Droste, Brian Kuhlman, Abdijapar Shamshiev, Serena Pellegatta, Nikolay V. Dokholyan and Gianpietro Dotti
    Cancer Immunol Res April 1 2021 9 (4) 441-453; DOI:10.1158/2326-6066.CIR-20-0451

    Structural analysis demonstrates that the instability of the scFv causes CAR self-aggregation and tonic signaling. Amino acid substitutions or humanization of the framework regions abrogates the tonic signaling and enhances the functionality of CAR-T cells.

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