Chronic lymphocytic leukemia (CLL) cells genetically modified to express B7-1, ICAM-1, and LFA-3 confer APC capacity to T cells from CLL patients.

Abstract

In chronic lymphocytic leukemia (CLL), malignant B cells and nonmalignant T cells exhibit dysfunction. We previously demonstrated that infection of CLL cells with modified vaccinia Ankara (MVA) expressing the costimulatory molecules B7-1, ICAM-1, and LFA-3 (designated TRICOM) increased expression of these costimulatory molecules on the surface of CLL cells and thus augmented their antigen-presenting capability. Here, we evaluate the effect of MVA-TRICOM-modified CLL cells on T cells. Following incubation with irradiated MVA-TRICOM-modified CLL cells, allogeneic and autologous CD4(+) and CD8(+) T cells expressed significantly higher levels of B7-1, ICAM-1, and LFA-3. We show that this increase was the result of physical acquisition from the antigen-presenting cells (APCs), and that purified T cells that acquired costimulatory molecules from MVA-TRICOM-modified CLL cells were able to stimulate the proliferation of untreated T cells. These results demonstrate for the first time that T cells from CLL patients can acquire multiple costimulatory molecules from autologous CLL cells and can then act as APCs themselves. Given the immunodeficiencies characteristic of CLL, enhancing the antigen-presenting function of CLL cells and T cells simultaneously could be a distinct advantage in the effort to elicit antitumor immune responses.

• Authors: Mary T Litzinger, Kenneth A Foon, Helen Sabzevari, Kwong-Yok Tsang, Jeffrey Schlom, Claudia Palena
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 58 Issue 6 Pg. 955-65 (Jun 2009) ISSN: 1432-0851 [Electronic] Germany
• PMID: 19009294 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• B7-1 Antigen
• CD58 Antigens
• RNA, Messenger
• Intercellular Adhesion Molecule-1

Topics

• Antigen-Presenting Cells (immunology)
• B7-1 Antigen (genetics, metabolism)
• CD58 Antigens (genetics, metabolism)
• Humans
• Intercellular Adhesion Molecule-1 (genetics, metabolism)
• Leukemia, Lymphocytic, Chronic, B-Cell (genetics, immunology)
• RNA, Messenger (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• T-Lymphocytes (immunology)
• Tumor Cells, Cultured
• Vaccinia virus (genetics)