Table of Contents

Research Articles

• Research Articles

  The IKZF1–IRF4/IRF5 Axis Controls Polarization of Myeloma-Associated Macrophages

  Dimitrios Mougiakakos, Christian Bach, Martin Böttcher, Fabian Beier, Linda Röhner, Andrej Stoll, Michael Rehli, Claudia Gebhard, Christopher Lischer, Martin Eberhardt, Julio Vera, Maike Büttner-Herold, Katrin Bitterer, Heidi Balzer, Magdalena Leffler, Simon Jitschin, Michael Hundemer, Mohamed H.S. Awwad, Martin Busch, Steffen Stenger, Simon Völkl, Christian Schütz, Jan Krönke, Andreas Mackensen and Heiko Bruns

  Cancer Immunol Res March 1 2021 9 (3) 265-278; DOI:10.1158/2326-6066.CIR-20-0555

  
  

  Lenalidomide treatment for multiple myeloma skews M2-like macrophages to an M1 phenotype because lenalidomide triggers IKZF1 degradation, increasing IRF5 expression and decreasing IRF4. Modulating IKZF1 levels might provide a way to control macrophage polarization for cancer treatment.
• Research Articles

  Antitumor Effects of CAR T Cells Redirected to the EDB Splice Variant of Fibronectin

  Jessica Wagner, Elizabeth Wickman, Timothy I. Shaw, Alejandro Allo Anido, Deanna Langfitt, Jinghui Zhang, Shaina N. Porter, Shondra M. Pruett-Miller, Heather Tillman, Giedre Krenciute and Stephen Gottschalk

  Cancer Immunol Res March 1 2021 9 (3) 279-290; DOI:10.1158/2326-6066.CIR-20-0280

  
  

  CAR T cells targeting the EDB splice variant of fibronectin, a pan-cancer solid tumor target, have potent antitumor activity in preclinical solid tumor models. They can target not only tumor cells but also the tumor vasculature.
• Research Articles

  ONCR-177, an Oncolytic HSV-1 Designed to Potently Activate Systemic Antitumor Immunity

  Brian B. Haines, Agnieszka Denslow, Peter Grzesik, Jennifer S. Lee, Terry Farkaly, Jacqueline Hewett, Daniel Wambua, Lingxin Kong, Prajna Behera, Judith Jacques, Caitlin Goshert, Michael Ball, Allison Colthart, Mitchel H. Finer, Melissa W. Hayes, Sonia Feau, Edward M. Kennedy, Lorena Lerner and Christophe Quéva

  Cancer Immunol Res March 1 2021 9 (3) 291-308; DOI:10.1158/2326-6066.CIR-20-0609

  
  

  ONCR-177 is a next-generation oncolytic virus being tested in the clinic. Preclinical efficacy and safety are reported and highlight the treatment's use as a single-agent, as well as in combination with immune checkpoint blockade.
• Research Articles

  IL1β Promotes Immune Suppression in the Tumor Microenvironment Independent of the Inflammasome and Gasdermin D

  Máté Kiss, Lieselotte Vande Walle, Pedro H.V. Saavedra, Els Lebegge, Helena Van Damme, Aleksandar Murgaski, Junbin Qian, Manuel Ehling, Samantha Pretto, Evangelia Bolli, Jiri Keirsse, Pauline M.R. Bardet, Sana M. Arnouk, Yvon Elkrim, Maryse Schmoetten, Jan Brughmans, Ayla Debraekeleer, Amelie Fossoul, Louis Boon, Geert Raes, Geert van Loo, Diether Lambrechts, Massimiliano Mazzone, Alain Beschin, Andy Wullaert, Mohamed Lamkanfi, Jo A. Van Ginderachter and Damya Laoui

  Cancer Immunol Res March 1 2021 9 (3) 309-323; DOI:10.1158/2326-6066.CIR-20-0431

  
  

  IL1β is implicated in cancer progression. The authors show that IL1β promotes neutrophil accumulation in tumors and suppresses antitumor immunity independently of the inflammasome, suggesting that therapeutic inflammasome inhibition will not limit IL1β production in certain cancer types.
• Research Articles

  The Tumor Microenvironment Impairs Th1 IFNγ Secretion through Alternative Splicing Modifications of Irf1 Pre-mRNA

  Antoine Bernard, Christophe Hibos, Corentin Richard, Etienne Viltard, Sandy Chevrier, Sophie Lemoine, Joséphine Melin, Etienne Humblin, Romain Mary, Théo Accogli, Fanny Chalmin, Mélanie Bruchard, Paul Peixoto, Eric Hervouet, Lionel Apetoh, François Ghiringhelli, Frédérique Végran and Romain Boidot

  Cancer Immunol Res March 1 2021 9 (3) 324-336; DOI:10.1158/2326-6066.CIR-19-0679

  
  

  TGFβ in the tumor microenvironment induces alternative splicing of the transcription factor IRF1, giving rise to a shortened isoform (IRF1Δ7) specifically in CD4⁺ Th1 cells. IRF1Δ7 inhibits Th1 IFNγ production, highlighting a potential target to boost antitumor responses.
• Research Articles

  A Machine Learning Approach Yields a Multiparameter Prognostic Marker in Liver Cancer

  Xiaoli Liu, Jilin Lu, Guanxiong Zhang, Junyan Han, Wei Zhou, Huan Chen, Henghui Zhang and Zhiyun Yang

  Cancer Immunol Res March 1 2021 9 (3) 337-347; DOI:10.1158/2326-6066.CIR-20-0616

  
  

  Using a machine learning–based strategy, a multiparametric prognostic model was developed. The constructed 20-feature gradient-boosting survival classifier reproducibly identifies patients with hepatocellular carcinoma (HCC) that are at the greatest risk of HCC-related death.
• Research Articles

  Notch-Regulated Dendritic Cells Restrain Inflammation-Associated Colorectal Carcinogenesis

  Lei Wang, Shuiliang Yu, Ernest R. Chan, Kai-Yuan Chen, Cui Liu, Danian Che, Amad Awadallah, Jay Myers, David Askew, Alex Y. Huang, Ivan Maillard, Dan Huang, Wei Xin and Lan Zhou

  Cancer Immunol Res March 1 2021 9 (3) 348-361; DOI:10.1158/2326-6066.CIR-20-0428

  
  

  Conventional dendritic cells (DC) play a key role in the anti-tumor immune response. The data show that Notch2 deletion in all cells or in only DCs promotes inflammation-associated colorectal carcinogenesis; targeting Notch2-controlled DCs could restrain colon cancer.