Table of Contents

Research Articles

• Research Articles

  CD96 Is an Immune Checkpoint That Regulates CD8⁺ T-cell Antitumor Function

  Deepak Mittal, Ailin Lepletier, Jason Madore, Amelia Roman Aguilera, Kimberley Stannard, Stephen J. Blake, Vicki L.J. Whitehall, Cheng Liu, Mark L. Bettington, Kazuyoshi Takeda, Georgina V. Long, Richard A. Scolyer, Ruth Lan, Nathan Siemers, Alan Korman, Michele W.L. Teng, Robert J. Johnston, William C. Dougall and Mark J. Smyth

  Cancer Immunol Res April 1 2019 7 (4) 559-571; DOI:10.1158/2326-6066.CIR-18-0637

  
  

  The antitumor activity of anti-CD96 monotherapy depends on several host factors, including CD8⁺ T cells and immune signaling. Inhibition of CD96 in combination with other immune checkpoint inhibitors shows superior antitumor activity over single or dual agent therapy.

• Research Articles

  Targeted Delivery of IL2 to the Tumor Stroma Potentiates the Action of Immune Checkpoint Inhibitors by Preferential Activation of NK and CD8⁺ T Cells

  Cornelia Hutmacher, Nicolás Gonzalo Núñez, Anna Rita Liuzzi, Burkhard Becher and Dario Neri

  Cancer Immunol Res April 1 2019 7 (4) 572-583; DOI:10.1158/2326-6066.CIR-18-0566

  
  

  Treatment of murine tumors with combination checkpoint blockade and an antibody-IL2 fusion protein reduces tumor growth, an effect dependent on CD8⁺ T cells and NK cells. These data support the use of engineered IL2 products for anti-cancer therapy.

• Research Articles | AuthorChoice

  Sustained Type I Interferon Reinforces NK Cell–Mediated Cancer Immunosurveillance during Chronic Virus Infection

  Ji Hoon Oh, Myeong Joon Kim, Seong Jin Choi, Young Ho Ban, Heung Kyu Lee, Eui-Cheol Shin, Kyung-Mi Lee and Sang-Jun Ha

  Cancer Immunol Res April 1 2019 7 (4) 584-599; DOI:10.1158/2326-6066.CIR-18-0403

  
  

  Chronic LCMV infection delays tumor progression as a result of sustained type I IFN signaling and enhanced NK cell–mediated immunosurveillance. This observation could improve the development of effective treatment strategies for cancer patients with chronic viral infections.

• Research Articles

  Regulatory T Cells in an Endogenous Mouse Lymphoma Recognize Specific Antigen Peptides and Contribute to Immune Escape

  Fatima Ahmetlić, Tanja Riedel, Nadine Hömberg, Vera Bauer, Nico Trautwein, Albert Geishauser, Tim Sparwasser, Stefan Stevanović, Martin Röcken and Ralph Mocikat

  Cancer Immunol Res April 1 2019 7 (4) 600-608; DOI:10.1158/2326-6066.CIR-18-0419

  
  

  In a mouse model of B-cell lymphoma, regulatory T cells suppressed antitumor responses. Treg cells recognized nonmutated self epitopes, which were characteristic of lymphoma and which were related to malignancy.

• Research Articles

  Automated Analysis of Lymphocytic Infiltration, Tumor Budding, and Their Spatial Relationship Improves Prognostic Accuracy in Colorectal Cancer

  Ines P. Nearchou, Kate Lillard, Christos G. Gavriel, Hideki Ueno, David J. Harrison and Peter D. Caie

  Cancer Immunol Res April 1 2019 7 (4) 609-620; DOI:10.1158/2326-6066.CIR-18-0377

  
  

  Automated image analysis reveals that high tumor bud numbers, low T-cell density, and few T cells proximal to tumor buds were associated with reduced survival of CRC patients. This model provided greater prognostic value than current clinical guidelines.

• Research Articles

  Intravesical Ty21a Vaccine Promotes Dendritic Cells and T Cell–Mediated Tumor Regression in the MB49 Bladder Cancer Model

  Sonia Domingos-Pereira, Karthik Sathiyanadan, Stefano La Rosa, Lenka Polák, Mathieu F. Chevalier, Paul Martel, Rim Hojeij, Laurent Derré, Jacques-Antoine Haefliger, Patrice Jichlinski and Denise Nardelli-Haefliger

  Cancer Immunol Res April 1 2019 7 (4) 621-629; DOI:10.1158/2326-6066.CIR-18-0671

  
  

  Low-dose intravesical administration of Ty21a, a commercial typhoid vaccine, generated effective antitumor DC and T-cell responses and improved survival in a mouse model of bladder cancer. These results demonstrate the potential of Ty21a for clinical use.

• Research Articles

  Low-Dose Apatinib Optimizes Tumor Microenvironment and Potentiates Antitumor Effect of PD-1/PD-L1 Blockade in Lung Cancer

  Sha Zhao, Shengxiang Ren, Tao Jiang, Bo Zhu, Xuefei Li, Chao Zhao, Yijun Jia, Jinpeng Shi, Limin Zhang, Xiaozhen Liu, Meng Qiao, Xiaoxia Chen, Chunxia Su, Hui Yu, Caicun Zhou, Jun Zhang, D. Ross Camidge and Fred R. Hirsch

  Cancer Immunol Res April 1 2019 7 (4) 630-643; DOI:10.1158/2326-6066.CIR-17-0640

  
  

  Both preclinical and phase IB clinical data indicate that lower-than-conventional doses of the anti-angiogenic agent apatinib (a VEGFR2-TKI) optimized the immunosuppressive tumor microenvironment and potentiated the therapeutic response to anti-PD-1/PD-L1 immunotherapy in lung cancer.

• Research Articles

  Immune Profiling and Quantitative Analysis Decipher the Clinical Role of Immune-Checkpoint Expression in the Tumor Immune Microenvironment of DLBCL

  Ziju Y. Xu-Monette, Min Xiao, Qingyan Au, Raghav Padmanabhan, Bing Xu, Nicholas Hoe, Sandra Rodríguez-Perales, Raul Torres-Ruiz, Ganiraju C. Manyam, Carlo Visco, Yi Miao, Xiaohong Tan, Hongwei Zhang, Alexandar Tzankov, Jing Wang, Karen Dybkær, Wayne Tam, Hua You, Govind Bhagat, Eric D. Hsi, Maurilio Ponzoni, Andrés J.M. Ferreri, Michael B. Møller, Miguel A. Piris, J. Han van Krieken, Jane N. Winter, Jason R. Westin, Lan V. Pham, L. Jeffrey Medeiros, George Z. Rassidakis, Yong Li, Gordon J. Freeman and Ken H. Young

  Cancer Immunol Res April 1 2019 7 (4) 644-657; DOI:10.1158/2326-6066.CIR-18-0439

  
  

  The immune profile of the tumor microenvironment in DLBCL patients was assessed with a MultiOmyx platform. PD-1/L1 expression on T cells and PD-L1 expression on macrophages had prognostic value in identification of patients with poor survival after immunochemotherapy.

• Research Articles

  Autologous Lymphocyte Infusion Supports Tumor Antigen Vaccine–Induced Immunity in Autologous Stem Cell Transplant for Multiple Myeloma

  Adam D. Cohen, Nikoletta Lendvai, Sarah Nataraj, Naoko Imai, Achim A. Jungbluth, Ioanna Tsakos, Adeeb Rahman, Anna Huo-Chang Mei, Herman Singh, Katarzyna Zarychta, Seunghee Kim-Schulze, Andrew Park, Ralph Venhaus, Katherine Alpaugh, Sacha Gnjatic and Hearn J. Cho

  Cancer Immunol Res April 1 2019 7 (4) 658-669; DOI:10.1158/2326-6066.CIR-18-0198

  
  

  Immunotherapy can include vaccines in the setting of autologous stem cell transplantation for multiple myeloma. Here, autologous lymphocyte infusion augmented immunotherapy and supported humoral and CD4⁺ helper T-cell immunity in response to a therapeutic tumor vaccine.

• Research Articles

  Radiotherapy and Cisplatin Increase Immunotherapy Efficacy by Enabling Local and Systemic Intratumoral T-cell Activity

  Paula Kroon, Elselien Frijlink, Victoria Iglesias-Guimarais, Andriy Volkov, Marit M. van Buuren, Ton N. Schumacher, Marcel Verheij, Jannie Borst and Inge Verbrugge

  Cancer Immunol Res April 1 2019 7 (4) 670-682; DOI:10.1158/2326-6066.CIR-18-0654

  
  

  The response to PD-1 blockade and CD137 agonism could be improved by “re-purposing” radiotherapy or cisplatin to modulate the tumor microenvironment. Chemo/radio-immunotherapy enhances CTL responses, tumor regression, and survival in a mouse model of poorly immunogenic breast cancer.

• Research Articles

  T-cell Activity against AML Improved by Dual-Targeted T Cells Stimulated through T-cell and IL7 Receptors

  Eric Krawczyk, Sergey N. Zolov, Kevin Huang and Challice L. Bonifant

  Cancer Immunol Res April 1 2019 7 (4) 683-692; DOI:10.1158/2326-6066.CIR-18-0748

  
  

  An engineered T cell specific for two antigens shows anti-AML activity. Combining CD123 recognition and IL7R activation enhances antitumor activity and T-cell survival in preclinical models, suggesting the value of extending this strategy to other tumor types.