Table of Contents

Research Articles

• Research Articles

  Collapse of the Plasmacytoid Dendritic Cell Compartment in Advanced Cutaneous Melanomas by Components of the Tumor Cell Secretome

  Raffaella Vescovi, Matilde Monti, Daniele Moratto, Lucia Paolini, Francesca Consoli, Luisa Benerini, Laura Melocchi, Stefano Calza, Mariella Chiudinelli, Giulio Rossi, Mattia Bugatti, Michele Maio, Ester Fonsatti, Camillo Farisoglio, Michele Simbolo, Camillo Almici, Rosanna Verardi, Aldo Scarpa, Paolo Bergese, Ausilia Manganoni, Fabio Facchetti and William Vermi

  Cancer Immunol Res January 1 2019 7 (1) 12-28; DOI:10.1158/2326-6066.CIR-18-0141

  
  

  Plasmacytoid dendritic cells (PDCs) can regulate anti-cancer immune responses. Factors in the melanoma secretome drive the PDC compartment to collapse during disease progression, and rescue of PDCs could aid existing spontaneous and drug-induced adaptive immune responses.

• Research Articles

  Batf3-Dependent Genes Control Tumor Rejection Induced by Dendritic Cells Independently of Cross-Presentation

  Derek J. Theisen, Stephen T. Ferris, Carlos G. Briseño, Nicole Kretzer, Arifumi Iwata, Kenneth M. Murphy and Theresa L. Murphy

  Cancer Immunol Res January 1 2019 7 (1) 29-39; DOI:10.1158/2326-6066.CIR-18-0138

  
  

  In addition to stabilizing cDC1 dendritic cell lineage commitment, BATF3 controls a set of genes required for cDC1 cells to promote tumor rejection. These BATF3-controlled genes, which are independent of cross-presentation, may be targets in the development of immunotherapies.

• Research Articles

  Leveraging TCR Affinity in Adoptive Immunotherapy against Shared Tumor/Self-Antigens

  Aaron M. Miller, Milad Bahmanof, Dietmar Zehn, Ezra E.W. Cohen and Stephen P. Schoenberger

  Cancer Immunol Res January 1 2019 7 (1) 40-49; DOI:10.1158/2326-6066.CIR-18-0371

  
  

  Adoptive cellular therapy (ACT) with a low-affinity T-cell receptor (TCR) that recognizes a self-antigen yields antitumor cytotoxicity but not autoimmune damage. A better understanding of TCR affinity could ultimately minimize autoimmunity while increasing ACT therapeutic efficacy.

• Research Articles

  High-Throughput Stability Screening of Neoantigen/HLA Complexes Improves Immunogenicity Predictions

  Dylan T. Blaha, Scott D. Anderson, Daniel M. Yoakum, Marlies V. Hager, Yuanyuan Zha, Thomas F. Gajewski and David M. Kranz

  Cancer Immunol Res January 1 2019 7 (1) 50-61; DOI:10.1158/2326-6066.CIR-18-0395

  
  

  Using a rapid, high-throughput method, peptide/HLA thermal stability was determined for a variety of peptides and peptide variants. This approach allows for predicting neoantigens that can best serve as targets for a robust T-cell response against cancer.

• Research Articles

  Mapping the MHC Class I–Spliced Immunopeptidome of Cancer Cells

  Juliane Liepe, John Sidney, Felix K.M. Lorenz, Alessandro Sette and Michele Mishto

  Cancer Immunol Res January 1 2019 7 (1) 62-76; DOI:10.1158/2326-6066.CIR-18-0424

  
  

  Unconventional spliced peptides can be presented by cancer cells. This survey of peptide characteristics in the immunopeptidome of colon and breast carcinoma cell lines may help to predict and identify an unforeseen pool of antigenic targets for immunotherapy.

• Research Articles | AuthorChoice

  Peripheral Blood TCR Repertoire Profiling May Facilitate Patient Stratification for Immunotherapy against Melanoma

  Sabrina A. Hogan, Anaïs Courtier, Phil F. Cheng, Nicoletta F. Jaberg-Bentele, Simone M. Goldinger, Manuarii Manuel, Solène Perez, Nadia Plantier, Jean-François Mouret, Thi Dan Linh Nguyen-Kim, Marieke I.G. Raaijmakers, Pia Kvistborg, Nicolas Pasqual, John B.A.G. Haanen, Reinhard Dummer and Mitchell P. Levesque

  Cancer Immunol Res January 1 2019 7 (1) 77-85; DOI:10.1158/2326-6066.CIR-18-0136

  
  

  Analysis of TCR repertoire clonality in blood samples collected from patients with melanoma before treatment may predict their eventual response to anti-PD1 and anti-CTLA4 therapy. Such a biomarker could help clinicians refine treatment courses for melanoma patients.

• Research Articles

  Computational Immune Monitoring Reveals Abnormal Double-Negative T Cells Present across Human Tumor Types

  Allison R. Greenplate, Daniel D. McClanahan, Brian K. Oberholtzer, Deon B. Doxie, Caroline E. Roe, Kirsten E. Diggins, Nalin Leelatian, Megan L. Rasmussen, Mark C. Kelley, Vivian Gama, Peter J. Siska, Jeffrey C. Rathmell, P. Brent Ferrell, Douglas B. Johnson and Jonathan M. Irish

  Cancer Immunol Res January 1 2019 7 (1) 86-99; DOI:10.1158/2326-6066.CIR-17-0692

  
  

  An analysis toolkit was developed for characterizing immunological changes over time in clinical samples. Use of this toolkit revealed the presence of a double-negative T-cell subset in melanoma, glioblastoma, and renal cell carcinoma but not in healthy tissues.

• Research Articles

  Phase I Trial of Autologous CAR T Cells Targeting NKG2D Ligands in Patients with AML/MDS and Multiple Myeloma

  Susanne H. Baumeister, Joana Murad, Lillian Werner, Heather Daley, Helene Trebeden-Negre, Joanina K. Gicobi, Adam Schmucker, Jake Reder, Charles L. Sentman, David E. Gilham, Frédéric F. Lehmann, Ilene Galinsky, Heidi DiPietro, Kristen Cummings, Nikhil C. Munshi, Richard M. Stone, Donna S. Neuberg, Robert Soiffer, Glenn Dranoff, Jerome Ritz and Sarah Nikiforow

  Cancer Immunol Res January 1 2019 7 (1) 100-112; DOI:10.1158/2326-6066.CIR-18-0307

  
  

  NKG2D-CAR T-cell therapy is safe and feasible. Infused cells were transiently detected and exhibited in vitro responses to autologous tumors. However, objective responses to low doses were only seen in lymphodepleted patients, warranting studies to improve efficacy.

• Research Articles

  Reduced Breast Tumor Growth after Immunization with a Tumor-Restricted MUC1 Glycopeptide Conjugated to Tetanus Toxoid

  Natascha Stergiou, Nikola Gaidzik, Anne-Sophie Heimes, Sarah Dietzen, Pol Besenius, Jörg Jäkel, Walburgis Brenner, Marcus Schmidt, Horst Kunz and Edgar Schmitt

  Cancer Immunol Res January 1 2019 7 (1) 113-122; DOI:10.1158/2326-6066.CIR-18-0256

  
  

  Tumor-associated MUC1 is a target for the development of breast cancer vaccines due to its tumor-specific overexpression and aberrant glycosylation. Immunization with synthetically produced tumor-associated MUC1 glycopeptides conjugated to tetanus toxoid resulted in reduced tumor burden in mice.

• Research Articles | AuthorChoice

  Calnexin Impairs the Antitumor Immunity of CD4⁺ and CD8⁺ T Cells

  Yichen Chen, Da Ma, Xi Wang, Juan Fang, Xiangqi Liu, Jingjing Song, Xinye Li, Xianyue Ren, Qiusheng Li, Qunxing Li, Shuqiong Wen, Liqun Luo, Juan Xia, Jun Cui, Gucheng Zeng, Lieping Chen, Bin Cheng and Zhi Wang

  Cancer Immunol Res January 1 2019 7 (1) 123-135; DOI:10.1158/2326-6066.CIR-18-0124

  
  

  T-cell numbers and effector functions are diminished by calnexin, an ER chaperone protein, possibly through PD-1 upregulation, in OSCC patients and in a mouse melanoma model. These results suggest calnexin could be targeted to improve immunotherapy responses.

• Research Articles | AuthorChoice

  PARP1 Suppresses the Transcription of PD-L1 by Poly(ADP-Ribosyl)ating STAT3

  Ling Ding, Xi Chen, Xiaqing Xu, Yuli Qian, Guikai Liang, Fengqi Yao, Zhangting Yao, Honghai Wu, Jieqiong Zhang, Qiaojun He and Bo Yang

  Cancer Immunol Res January 1 2019 7 (1) 136-149; DOI:10.1158/2326-6066.CIR-18-0071

  
  

  PARP1-mediated poly(ADP-ribosyl)ation of STAT3 drives its dephosphorylation, leading to the inhibition of PD-L1 transcription across multiple cancer types. In patients, PARP1 and PD-L1 expression are inversely correlated. These data highlight a conserved regulatory mechanism for PD-L1 expression.

• Research Articles

  PD-L1 microSPECT/CT Imaging for Longitudinal Monitoring of PD-L1 Expression in Syngeneic and Humanized Mouse Models for Cancer

  Sandra Heskamp, Peter J. Wierstra, Janneke D.M. Molkenboer-Kuenen, Gerwin W. Sandker, Soley Thordardottir, Jeannette Cany, Daniel Olive, Johan Bussink, Otto C. Boerman, Harry Dolstra, Erik H.J.G. Aarntzen and Willemijn A. Hobo

  Cancer Immunol Res January 1 2019 7 (1) 150-161; DOI:10.1158/2326-6066.CIR-18-0280

  
  

  PD-L1 microSPECT/CT is a technique to detect PD-L1 expression in syngeneic murine models and humanized mice, allowing the monitoring of therapy-induced changes in tumor PD-L1 expression. In the future, this technique could enable patient selection for PD-1/PD-L1-targeted therapies.