Table of Contents

Research Articles

• Research Articles

  RORγ Agonists Enhance the Sustained Antitumor Activity through Intrinsic Tc17 Cytotoxicity and Tc1 Recruitment

  Xikui Liu, Elizabeth M. Zawidzka, Hongxiu Li, Charles A. Lesch, Jenna Dunbar, Dick Bousley, Weiping Zou, Xiao Hu and Laura L. Carter

  Cancer Immunol Res July 1 2019 7 (7) 1054-1063; DOI:10.1158/2326-6066.CIR-18-0714

  
  

  Tumor evasion can ensue from too few infiltrating cytotoxic T cells—type 1 (Tc1) or 17 (Tc17)—or infiltration of dysfunctional effectors. RORγ agonists augmented Tc17 survival and lytic activity and directed recruitment of other functional effector cells.

• Research Articles | AuthorChoice

  Targeting Hypoxia-Induced Carbonic Anhydrase IX Enhances Immune-Checkpoint Blockade Locally and Systemically

  Shawn C. Chafe, Paul C. McDonald, Saeed Saberi, Oksana Nemirovsky, Geetha Venkateswaran, Samantha Burugu, Dongxia Gao, Alberto Delaidelli, Alastair H. Kyle, Jennifer H.E. Baker, Jordan A. Gillespie, Ali Bashashati, Andrew I. Minchinton, Youwen Zhou, Sohrab P. Shah and Shoukat Dedhar

  Cancer Immunol Res July 1 2019 7 (7) 1064-1078; DOI:10.1158/2326-6066.CIR-18-0657

  
  

  The prognosis for breast cancer and melanoma patients is worse if their tumors metabolically regulate pH, promoting an acidic microenvironment, through enzymes like CAIX. Inhibition of CAIX plus blockade of immune checkpoints boosts antitumor responses by buffering acidosis.

• Research Articles

  Hypoxia-Induced VISTA Promotes the Suppressive Function of Myeloid-Derived Suppressor Cells in the Tumor Microenvironment

  Jie Deng, Jiannan Li, Aurelien Sarde, J. Louise Lines, Yu-Chi Lee, David C. Qian, Dov A. Pechenick, Richard Manivanh, Isabelle Le Mercier, Christopher H. Lowrey, Frederick S. Varn, Chao Cheng, David A. Leib, Randolph J. Noelle and Rodwell Mabaera

  Cancer Immunol Res July 1 2019 7 (7) 1079-1090; DOI:10.1158/2326-6066.CIR-18-0507

  
  

  VISTA, induced on MDSCs by hypoxia in the tumor microenvironment, enhances suppression of both CD4⁺ and CD8⁺ T cells. This mechanism of hypoxia-driven immune escape and checkpoint resistance suggests a translatable approach to combination therapies.

• Research Articles

  Tumor Cells Hijack Macrophage-Produced Complement C1q to Promote Tumor Growth

  Lubka T. Roumenina, Marie V. Daugan, Rémi Noé, Florent Petitprez, Yann A. Vano, Rafaël Sanchez-Salas, Etienne Becht, Julie Meilleroux, Bénédicte Le Clec'h, Nicolas A. Giraldo, Nicolas S. Merle, Cheng-Ming Sun, Virginie Verkarre, Pierre Validire, Janick Selves, Laetitia Lacroix, Olivier Delfour, Isabelle Vandenberghe, Celine Thuilliez, Sonia Keddani, Imene B. Sakhi, Eric Barret, Pierre Ferré, Nathalie Corvaïa, Alexandre Passioukov, Eric Chetaille, Marina Botto, Aurélien de Reynies, Stephane Marie Oudard, Arnaud Mejean, Xavier Cathelineau, Catherine Sautès-Fridman and Wolf H. Fridman

  Cancer Immunol Res July 1 2019 7 (7) 1091-1105; DOI:10.1158/2326-6066.CIR-18-0891

  
  

  The density of C1q-producing TAMs and C4d deposits, hallmarks of complement activation, are negative prognostic factors in human clear-cell renal cell carcinoma. Thus, the classical complement pathway is a potential therapeutic target for this cancer.

• Research Articles | AuthorChoice

  Combination Therapy for Treating Advanced Drug-Resistant Acute Lymphoblastic Leukemia

  Yorleny Vicioso, Hermann Gram, Rose Beck, Abhishek Asthana, Keman Zhang, Derek P. Wong, John Letterio and Reshmi Parameswaran

  Cancer Immunol Res July 1 2019 7 (7) 1106-1119; DOI:10.1158/2326-6066.CIR-19-0058

  
  

  Blocking BAFF-R early in ALL promotes killing of leukemic cells. However, if given at later disease stages, efficacy is limited due to TGFβ. Combining VAY736 and a TGFβR1 inhibitor improved treatment efficacy in advanced and drug-resistant ALL.

• Research Articles

  Inhibition of the NKp44-PCNA Immune Checkpoint Using a mAb to PCNA

  Kiran Kundu, Susmita Ghosh, Rhitajit Sarkar, Avishay Edri, Michael Brusilovsky, Orly Gershoni-Yahalom, Rami Yossef, Avishai Shemesh, Jean-Charles Soria, Vladimir Lazar, Ben-Zion Joshua, Kerry S. Campbell, Moshe Elkabets and Angel Porgador

  Cancer Immunol Res July 1 2019 7 (7) 1120-1134; DOI:10.1158/2326-6066.CIR-19-0023

  
  

  An immune checkpoint blocking antibody was developed against cancer cell surface PCNA, a ligand for NK-cell protein NKp44. Tests of the antibody in mice bearing patient-derived xenografts showed promise for overcoming tumor resistance to immunotherapy.

• Research Articles

  Targeting the YB-1/PD-L1 Axis to Enhance Chemotherapy and Antitumor Immunity

  Zhen Tao, Hailong Ruan, Lin Sun, Dong Kuang, Yongchun Song, Qi Wang, Tao Wang, Yi Hao and Ke Chen

  Cancer Immunol Res July 1 2019 7 (7) 1135-1147; DOI:10.1158/2326-6066.CIR-18-0648

  
  

  The YB-1 signaling axis promotes tumor immune evasion and multidrug resistance. When targeted, chemoresistance decreased and antitumor responses were enhanced, suggesting an avenue for treating tumor multidrug resistance and immunosuppressive tumor microenvironments.

• Research Articles

  Reduced Neoantigen Expression Revealed by Longitudinal Multiomics as a Possible Immune Evasion Mechanism in Glioma

  Takahide Nejo, Hirokazu Matsushita, Takahiro Karasaki, Masashi Nomura, Kuniaki Saito, Shota Tanaka, Shunsaku Takayanagi, Taijun Hana, Satoshi Takahashi, Yosuke Kitagawa, Tsukasa Koike, Yukari Kobayashi, Genta Nagae, Shogo Yamamoto, Hiroki Ueda, Kenji Tatsuno, Yoshitaka Narita, Motoo Nagane, Keisuke Ueki, Ryo Nishikawa, Hiroyuki Aburatani, Akitake Mukasa, Nobuhito Saito and Kazuhiro Kakimi

  Cancer Immunol Res July 1 2019 7 (7) 1148-1161; DOI:10.1158/2326-6066.CIR-18-0599

  
  

  Whole exome and RNA sequencing of paired primary and recurrent glioma specimens revealed decreased neoantigen expression at recurrence. Evidence of persistent immune responses suggests immune selection pressure as a possible mechanism, despite treatment with standard, nonimmune-based regimens.

• Research Articles | AuthorChoice

  A Gene Signature Predicting Natural Killer Cell Infiltration and Improved Survival in Melanoma Patients

  Joseph Cursons, Fernando Souza-Fonseca-Guimaraes, Momeneh Foroutan, Ashley Anderson, Frédéric Hollande, Soroor Hediyeh-Zadeh, Andreas Behren, Nicholas D. Huntington and Melissa J. Davis

  Cancer Immunol Res July 1 2019 7 (7) 1162-1174; DOI:10.1158/2326-6066.CIR-18-0500

  
  

  Innate immunity can provide new targets for immunotherapy. Singscore, a gene-set scoring method, revealed that NK cell infiltration correlated with improved patient survival rates. Stromal and tumor elements, as well as cytokines involved in NK function were investigated.

• Research Articles

  CCR4 Blockade Depletes Regulatory T Cells and Prolongs Survival in a Canine Model of Bladder Cancer

  Shingo Maeda, Kohei Murakami, Akiko Inoue, Tomohiro Yonezawa and Naoaki Matsuki

  Cancer Immunol Res July 1 2019 7 (7) 1175-1187; DOI:10.1158/2326-6066.CIR-18-0751

  
  

  Anti-CCR4 treatment to target regulatory T cells induced clinical responses and prolonged survival in dogs with spontaneous bladder cancer. Expression of CCR4 in human tumor samples suggests translational relevance for treatment of bladder cancer in humans.

• Research Articles

  An Artificial Antigen-Presenting Cell Delivering 11 Immune Molecules Expands Tumor Antigen–Specific CTLs in Ex Vivo and In Vivo Murine Melanoma Models

  Lei Zhang, Shilong Song, Xiaoxiao Jin, Xin Wan, Khawar Ali Shahzad, Weiya Pei, Chen Zhao and Chuanlai Shen

  Cancer Immunol Res July 1 2019 7 (7) 1188-1201; DOI:10.1158/2326-6066.CIR-18-0881

  
  

  Multipotent microparticles bearing T-cell antigens and costimulatory molecules—and containing cytokines, chemokines, and checkpoint inhibitors—were injected intravenously into melanoma-bearing mice. These particles inhibited melanoma growth and expanded tumor-specific CTLs in peripheral blood, spleen, and tumor tissue.

• Research Articles | AuthorChoice

  HPV Epitope Processing Differences Correlate with ERAP1 Allotype and Extent of CD8⁺ T-cell Tumor Infiltration in OPSCC

  Emma Reeves, Oliver Wood, Christian H. Ottensmeier, Emma V. King, Gareth J. Thomas, Tim Elliott and Edward James

  Cancer Immunol Res July 1 2019 7 (7) 1202-1213; DOI:10.1158/2326-6066.CIR-18-0498

  
  

  The ability to generate HPV-derived peptide antigens is governed by which ERAP1 molecules are expressed. Thus HPV⁺ OPSCC patients have different numbers of tumor-infiltrating CD8⁺ T cells, which affects disease progression.

• Research Articles

  The Impact of High-Dose Glucocorticoids on the Outcome of Immune-Checkpoint Inhibitor–Related Thyroid Disorders

  Chanjuan Ma, F. Stephen Hodi, Anita Giobbie-Hurder, Xiaocheng Wang, Jing Zhou, Amy Zhang, Ying Zhou, Fei Mao, Trevor E. Angell, Chelsea P. Andrews, Jiani Hu, Romualdo Barroso-Sousa, Ursula B. Kaiser, Sara M. Tolaney and Le Min

  Cancer Immunol Res July 1 2019 7 (7) 1214-1220; DOI:10.1158/2326-6066.CIR-18-0613

  
  

  Thyroid disorders are common immune-related adverse events, and improved clinical management is needed. In this study, high dose glucocorticoids did not improve duration of thyrotoxicosis or onset of hypothyroidism in patients treated with immune checkpoint inhibitors.