Table of Contents

Research Articles

• Research Articles

  Tumor- and Neoantigen-Reactive T-cell Receptors Can Be Identified Based on Their Frequency in Fresh Tumor

  Anna Pasetto, Alena Gros, Paul F. Robbins, Drew C. Deniger, Todd D. Prickett, Rodrigo Matus-Nicodemos, Daniel C. Douek, Bryan Howie, Harlan Robins, Maria R. Parkhurst, Jared Gartner, Katarzyna Trebska-McGowan, Jessica S. Crystal and Steven A. Rosenberg

  Cancer Immunol Res September 2 2016 4 (9) 734-743; DOI:10.1158/2326-6066.CIR-16-0001

  
  

  Effective adoptive T-cell therapy requires multiple tumor-epitope reactive T-cell clones. Fresh TILs were found to frequently contain such cells. Their TCRs were rapidly isolated based only on their frequency and could be used for personalized TCR-gene therapy.

• Research Articles

  Local Tumor Treatment in Combination with Systemic Ipilimumab Immunotherapy Prolongs Overall Survival in Patients with Advanced Malignant Melanoma

  Sebastian Theurich, Sacha I. Rothschild, Michael Hoffmann, Mario Fabri, Andrea Sommer, Maria Garcia-Marquez, Martin Thelen, Catherine Schill, Ramona Merki, Thomas Schmid, Dieter Koeberle, Alfred Zippelius, Christian Baues, Cornelia Mauch, Christian Tigges, Alexander Kreuter, Jan Borggrefe, Michael von Bergwelt-Baildon and Max Schlaak

  Cancer Immunol Res September 2 2016 4 (9) 744-754; DOI:10.1158/2326-6066.CIR-15-0156

  
  

  Too few patients benefit from immune checkpoint inhibition alone. However, patients with melanoma receiving systemic anti-CTLA-4 plus localized treatments had significantly prolonged overall survival. In a multivariate analysis, adding local treatment was an independent factor for improved survival.

• Research Articles

  Analyses of Pretherapy Peripheral Immunoscore and Response to Vaccine Therapy

  Benedetto Farsaci, Renee N. Donahue, Italia Grenga, Lauren M. Lepone, Peter S. Kim, Brendan Dempsey, Janet C. Siebert, Nuhad K. Ibrahim, Ravi A. Madan, Christopher R. Heery, James L. Gulley and Jeffrey Schlom

  Cancer Immunol Res September 2 2016 4 (9) 755-765; DOI:10.1158/2326-6066.CIR-16-0037

  
  

  Refined subsets of peripheral blood immune cells were assessed prior to therapy in two clinical trials. The resultant “peripheral immunoscores,” compiled through methodology potentially generalizable to other trials, were correlated with clinical benefit in patients receiving vaccine therapy.

• Research Articles | AuthorChoice

  Gp96-Ig/Costimulator (OX40L, ICOSL, or 4-1BBL) Combination Vaccine Improves T-cell Priming and Enhances Immunity, Memory, and Tumor Elimination

  George Fromm, Suresh de Silva, Louise Giffin, Xin Xu, Jason Rose and Taylor H. Schreiber

  Cancer Immunol Res September 2 2016 4 (9) 766-778; DOI:10.1158/2326-6066.CIR-15-0228

  
  

  Local anticancer therapies can increase antitumor efficacy while reducing toxicities. Cellular vaccines that locally secreted costimulation ligands produced stronger, more specific T-cell activation and tumor rejection with lower ligand concentrations than did vaccines combined with systemic antibody agonists.

• Research Articles

  Myeloma Drug Resistance Induced by Binding of Myeloma B7-H1 (PD-L1) to PD-1

  Mariko Ishibashi, Hideto Tamura, Mika Sunakawa, Asaka Kondo-Onodera, Namiko Okuyama, Yasuko Hamada, Keiichi Moriya, Inhak Choi, Koji Tamada and Koiti Inokuchi

  Cancer Immunol Res September 2 2016 4 (9) 779-788; DOI:10.1158/2326-6066.CIR-15-0296

  
  

  B7-H1 suppresses T cells by binding to PD-1, but it is unclear how binding to B7-H1 on cancer cells affects tumors. “Reverse signaling” of B7-H1 on myeloma cells was found to induce drug resistance through the Akt-signaling pathway.

• Research Articles

  Mutation Drivers of Immunological Responses to Cancer

  Eduard Porta-Pardo and Adam Godzik

  Cancer Immunol Res September 2 2016 4 (9) 789-798; DOI:10.1158/2326-6066.CIR-15-0233

  
  

  Tumor mutations create neoantigens that increase their immunogenicity but also enable new avenues of immune escape. DomainXplorer analyzes distributions of mutations in cancer genomes searching for correlations with immune response that are not seen by gene level methods.

• Research Articles

  Molecular Programming of Tumor-Infiltrating CD8⁺ T Cells and IL15 Resistance

  Andrew L. Doedens, Mark P. Rubinstein, Emilie T. Gross, J. Adam Best, David H. Craig, Megan K. Baker, David J. Cole, Jack D. Bui and Ananda W. Goldrath

  Cancer Immunol Res September 2 2016 4 (9) 799-811; DOI:10.1158/2326-6066.CIR-15-0178

  
  

  Tumor-infiltrating CD8⁺ T cells were profoundly resistant to IL15 complexes, so could not induce tumor regression. Their gene-expression signature was compared with that of productive cytotoxic responses and known differentiation states to determine how to restore antitumor function and cytokine responsiveness.