Converting Lymphoma Cells into Potent Antigen-Presenting Cells for Interferon-Induced Tumor Regression

Cancer Immunol Res. 2017 Jul;5(7):560-570. doi: 10.1158/2326-6066.CIR-16-0221. Epub 2017 May 22.


Anti-hCD20 is a therapeutic mAb that is clinically used to treat B-cell lymphoma. Some lymphomas are resistant to anti-hCD20; others relapse after treatment with anti-hCD20. Using a syngeneic immunocompetent mouse model, we observed that targeting lymphoma with interferon-α (IFNα) abolished resistance of B-cell lymphoma to anti-CD20 while limiting interferon (IFN)-associated systemic toxicity in the host. Control of tumors by a fusion of anti-CD20 and IFNα (anti-CD20-IFNα) depended on existing tumor-infiltrating CD8+ T cells. Although lymphomas were resistant to IFN-directed killing, IFN-exposed tumor cells became the dominant antigen-presenting cells (APC) for the reactivation of tumor-infiltrating CD8+ T cells that then controlled those lymphomas. Anti-CD20-IFNα also abolished checkpoint blockade resistance in advanced B-cell lymphoma. Our findings indicate that anti-CD20-IFNα eradicates B-cell lymphoma by employing tumor cells as APCs to reactivate tumor-infiltrating CD8+ T cells and synergizing with anti-PD-L1 treatment. Cancer Immunol Res; 5(7); 560-70. ©2017 AACR.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigen-Presenting Cells / drug effects
  • Antigen-Presenting Cells / immunology*
  • Antigens, CD20 / genetics
  • Antigens, CD20 / immunology*
  • Antigens, CD20 / therapeutic use
  • B7-H1 Antigen / immunology
  • B7-H1 Antigen / therapeutic use
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • Drug Resistance, Neoplasm / genetics
  • Drug Resistance, Neoplasm / immunology
  • Humans
  • Interferon-alpha / genetics
  • Interferon-alpha / immunology*
  • Interferon-alpha / therapeutic use
  • Lymphocytes, Tumor-Infiltrating / drug effects
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphoma, B-Cell / drug therapy*
  • Lymphoma, B-Cell / genetics
  • Lymphoma, B-Cell / immunology
  • Mice
  • Neoplasm Recurrence, Local / immunology
  • Neoplasm Recurrence, Local / therapy
  • Rituximab / administration & dosage
  • Rituximab / immunology


  • Antigens, CD20
  • B7-H1 Antigen
  • Cd274 protein, mouse
  • Interferon-alpha
  • Rituximab