Table of Contents

Research Articles

• Research Articles | AuthorChoice

  Excessive Costimulation Leads to Dysfunction of Adoptively Transferred T Cells

  Dinali Wijewarnasuriya, Christina Bebernitz, Andrea V. Lopez, Sarwish Rafiq and Renier J. Brentjens

  Cancer Immunol Res June 1 2020 8 (6) 732-742; DOI:10.1158/2326-6066.CIR-19-0908

  
  

  CAR T cells can be driven into a dysfunctional state through excessive costimulation. Understanding the limits of costimulation for CAR T cells will aid design of more efficacious CAR T cells for future clinical trials.
• Research Articles | AuthorChoice

  Optimization of T-cell Receptor–Modified T Cells for Cancer Therapy

  Dylan J. Drakes, Sarwish Rafiq, Terence J. Purdon, Andrea V. Lopez, Smita S. Chandran, Christopher A. Klebanoff and Renier J. Brentjens

  Cancer Immunol Res June 1 2020 8 (6) 743-755; DOI:10.1158/2326-6066.CIR-19-0910

  
  

  Tumor-directed T cells function better when expressing IL18 rather than IL12. TCR-modified T cells secreting IL18 eradicate established tumors in syngeneic models in combination with sublethal irradiation and in xenograft models, providing evidence to support IL18-boosted T-cell clinical trials.
• Research Articles

  Donor Lymphocyte–Derived Natural Killer Cells Control MHC Class I–Negative Melanoma

  Nana Dang, Yuan Lin, Mark Waer and Ben Sprangers

  Cancer Immunol Res June 1 2020 8 (6) 756-768; DOI:10.1158/2326-6066.CIR-19-0666

  
  

  Donor lymphocyte infusion after allogenic bone marrow transplantation can promote antitumor immunity but risks graft-versus-host disease. If there is no prior marrow transplantation, then donor lymphocyte infusion allows donor NK cells to control MHC-negative melanoma without toxicity.
• Research Articles

  Inhibition of MICA and MICB Shedding Elicits NK-Cell–Mediated Immunity against Tumors Resistant to Cytotoxic T Cells

  Lucas Ferrari de Andrade, Sushil Kumar, Adrienne M. Luoma, Yoshinaga Ito, Pedro Henrique Alves da Silva, Deng Pan, Jason W. Pyrdol, Charles H. Yoon and Kai W. Wucherpfennig

  Cancer Immunol Res June 1 2020 8 (6) 769-780; DOI:10.1158/2326-6066.CIR-19-0483

  
  

  Tumor cells evade NK-cell–mediated immunity by proteolytic shedding of the activating MICA/B ligands. Use of a MICA/B antibody inhibits MICA/B proteolytic shedding, leading to NK-cell responses against tumor cells resistant to cytotoxic T cells.
• Research Articles | AuthorChoice

  CD137/OX40 Bispecific Antibody Induces Potent Antitumor Activity that Is Dependent on Target Coengagement

  Miguel Gaspar, John Pravin, Leonor Rodrigues, Sandra Uhlenbroich, Katy L. Everett, Francisca Wollerton, Michelle Morrow, Mihriban Tuna and Neil Brewis

  Cancer Immunol Res June 1 2020 8 (6) 781-793; DOI:10.1158/2326-6066.CIR-19-0798

  
  

  Antibody agonists that target T-cell costimulatory pathways are being tested in the clinic. FS120, a dual agonist antibody specific for CD137 and OX40, delays tumor growth by improving the activation and proliferation of peripheral T cells.
• Research Articles

  Histone Deacetylase Inhibitors and IL21 Cooperate to Reprogram Human Effector CD8⁺ T Cells to Memory T Cells

  Junmei Wang, Farah Hasan, Amanda C. Frey, Haiyan S. Li, Jungsun Park, Ke Pan, Cara Haymaker, Chantale Bernatchez, Dean A. Lee, Stephanie S. Watowich and Cassian Yee

  Cancer Immunol Res June 1 2020 8 (6) 794-805; DOI:10.1158/2326-6066.CIR-19-0619

  
  

  Improving the in vivo persistence of adoptive cell therapies correlates to better patient responses. Histone deacetylase inhibitors and IL21 shift CD8⁺ T cells to a more persistent, central memory phenotype by increasing CD28 promoter accessibility.
• Research Articles

  Anti-VEGF Treatment Enhances CD8⁺ T-cell Antitumor Activity by Amplifying Hypoxia

  Patricia E. de Almeida, Judy Mak, Genevive Hernandez, Rajiv Jesudason, Aurelie Herault, Vincent Javinal, Jovencio Borneo, Jeong M. Kim and Kevin B. Walsh

  Cancer Immunol Res June 1 2020 8 (6) 806-818; DOI:10.1158/2326-6066.CIR-19-0360

  
  

  Amplification of tumor hypoxia by anti-VEGF treatment enhances CD8⁺ T-cell antitumor responses through increased HIF1α activity. Combining anti-angiogenics and immunotherapeutics may be useful for the treatment of cancer.
• Research Articles

  Quantification of Early-Stage Myeloid-Derived Suppressor Cells in Cancer Requires Excluding Basophils

  ANM Nazmul H. Khan, Tiffany R. Emmons, Jerry T. Wong, Emad Alqassim, Kelly L. Singel, Jaron Mark, Brandon E. Smith, Joseph D. Tario, Kevin H. Eng, Kirsten B. Moysich, Kunle Odunsi, Scott I. Abrams and Brahm H. Segal

  Cancer Immunol Res June 1 2020 8 (6) 819-828; DOI:10.1158/2326-6066.CIR-19-0556

  
  

  A substantial proportion of cells with early-stage myeloid-derived suppressor cell (e-MDSC) surface markers in circulation and in ascites of patients with ovarian cancer are basophils. Exclusion of basophils from e-MDSC is required for prognostic and therapeutic studies.
• Research Articles

  CSF1R Is Required for Differentiation and Migration of Langerhans Cells and Langerhans Cell Histiocytosis

  Silvia Lonardi, Sara Scutera, Sara Licini, Luisa Lorenzi, Anna Maria Cesinaro, Luisa Benerini Gatta, Carlotta Castagnoli, Daniele Bollero, Rosaria Sparti, Michela Tomaselli, Daniela Medicina, Federica Calzetti, Marco Antonio Cassatella, Fabio Facchetti, Tiziana Musso and William Vermi

  Cancer Immunol Res June 1 2020 8 (6) 829-841; DOI:10.1158/2326-6066.CIR-19-0232

  
  

  CSF1R promotes efficient Langerhans cell (LC) differentiation from hematopoietic progenitors and migration, which may be reduced by CSF1R kinase inhibition. CSF1R expression in clinical LC histiocytosis (LCH) specimens suggests potential for CSF1R blockade in the treatment of LCH.