Overcoming the Immunosuppressive Tumor Microenvironment of Hodgkin Lymphoma Using Chimeric Antigen Receptor T Cells

Cancer Discov. 2017 Oct;7(10):1154-1167. doi: 10.1158/2159-8290.CD-16-0850. Epub 2017 Jun 2.


Patients with otherwise treatment-resistant Hodgkin lymphoma could benefit from chimeric antigen receptor T-cell (CART) therapy. However, Hodgkin lymphoma lacks CD19 and contains a highly immunosuppressive tumor microenvironment (TME). We hypothesized that in Hodgkin lymphoma, CART should target both malignant cells and the TME. We demonstrated CD123 on both Hodgkin lymphoma cells and TME, including tumor-associated macrophages (TAM). In vitro, Hodgkin lymphoma cells convert macrophages toward immunosuppressive TAMs that inhibit T-cell proliferation. In contrast, anti-CD123 CART recognized and killed TAMs, thus overcoming immunosuppression. Finally, we showed in immunodeficient mouse models that CART123 eradicated Hodgkin lymphoma and established long-term immune memory. A novel platform that targets malignant cells and the microenvironment may be needed to successfully treat malignancies with an immunosuppressive milieu.Significance: Anti-CD123 chimeric antigen receptor T cells target both the malignant cells and TAMs in Hodgkin lymphoma, thereby eliminating an important immunosuppressive component of the tumor microenvironment. Cancer Discov; 7(10); 1154-67. ©2017 AACR.This article is highlighted in the In This Issue feature, p. 1047.

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Line, Tumor
  • Gene Expression Profiling / methods
  • Hodgkin Disease / immunology
  • Hodgkin Disease / therapy*
  • Humans
  • Interleukin-3 Receptor alpha Subunit / metabolism*
  • K562 Cells
  • Macrophages / cytology
  • Macrophages / immunology*
  • Macrophages / pathology
  • Mice
  • Recombinant Fusion Proteins / metabolism*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / transplantation*
  • Tumor Microenvironment


  • IL3RA protein, human
  • Interleukin-3 Receptor alpha Subunit
  • Recombinant Fusion Proteins