Immunosuppressive effects of multiple myeloma are overcome by PD-L1 blockade

Biol Blood Marrow Transplant. 2011 Aug;17(8):1133-45. doi: 10.1016/j.bbmt.2011.03.011. Epub 2011 Apr 12.


Multiple myeloma is an incurable plasma cell malignancy. Patients who fail conventional therapy are frequently treated with hematopoietic stem cell transplantation (HSCT), which results in reduced tumor burden, but the patients subsequently relapse from sites of chemotherapy-resistant disease. Using the 5T33 murine model of myeloma and a previously successful immunotherapy regimen consisting of autologous (syngeneic) HSCT and cell-based vaccine administration, we were unable to improve survival of myeloma-bearing mice. The 5T33 tumor line, similar to malignant plasma cells from myeloma patients, expresses high levels of programmed death receptor ligand-1 (PD-L1), which binds to the inhibitory receptor, PD-1. We observed that T cells from myeloma-bearing mice express high levels of PD-1, which has also been observed in patients with multiple myeloma. These PD-1(+) T cells were exhausted and produced IL-10. Based on these observations, we combined HSCT with whole-cell vaccination and PD-L1 blockade. Inhibition of the PD-1/PD-L1 pathway with HSCT and whole-cell vaccination increased the survival of myeloma-bearing mice from 0% to 40%. These data demonstrate a role for PD-L1 in suppressing immune responses to myeloma and suggest that blockade of this pathway may enhance immunotherapy for this disease.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology*
  • Apoptosis / immunology
  • B7-H1 Antigen / antagonists & inhibitors*
  • B7-H1 Antigen / biosynthesis
  • B7-H1 Antigen / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Line, Tumor
  • Disease Models, Animal
  • Female
  • Hematopoietic Stem Cell Transplantation
  • Hepatitis A Virus Cellular Receptor 2
  • Humans
  • Immunologic Memory
  • Immunosuppressive Agents / immunology
  • Immunosuppressive Agents / pharmacology*
  • Killer Cells, Natural / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Multiple Myeloma / immunology*
  • Multiple Myeloma / pathology
  • Multiple Myeloma / therapy*
  • Plasma Cells / immunology
  • Plasma Cells / pathology
  • Receptors, Virus / biosynthesis
  • Receptors, Virus / immunology


  • Antibodies, Monoclonal
  • B7-H1 Antigen
  • Cd274 protein, mouse
  • Havcr2 protein, mouse
  • Hepatitis A Virus Cellular Receptor 2
  • Immunosuppressive Agents
  • Receptors, Virus