The frequency of T regulatory cells modulates the survival of multiple myeloma patients: detailed characterisation of immune status in multiple myeloma

• Published in: British journal of cancer 2012-01, Vol.106 (3), p.546-552
• Main Authors: Giannopoulos, K, Kaminska, W, Hus, I, Dmoszynska, A
• Format: Article
• Language: English
• Subjects: 692/698/1543/1565/133; 692/698/1543/1565/1597/554/1898/1271; 692/699/67/1059/99; 692/699/67/1990/804; Adult; Aged; Aged, 80 and over; Antigen presentation; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Bone marrow; Cancer Research; Case-Control Studies; Chemotherapy; Cytokines - blood; Dendritic cells; Dendritic Cells - immunology; Drug Resistance; Epidemiology; Female; Forkhead Transcription Factors - metabolism; Humans; Immune system; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulinopathies; Immunopathology; Immunophenotyping; Interleukin-10 - blood; Interleukin-10 - immunology; Interleukin-6 - blood; Interleukin-6 - immunology; Lymphocytes; Male; Medical research; Medical sciences; Middle Aged; Molecular Diagnostics; Molecular Medicine; Multiple myeloma; Multiple Myeloma - immunology; Multiple Myeloma - mortality; Oncology; Stem cell transplantation; T-Lymphocyte Subsets - immunology; T-Lymphocytes, Regulatory - immunology; Transforming Growth Factor beta - blood; Transforming Growth Factor beta - immunology; Tumors
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2011.575

Background: Multiple myeloma (MM) is an immunoproliferative disease characterised by the uncontrolled proliferation of plasma cells, which is accompanied by defects in the immune system. Methods: This study aimed to characterise the frequency of T regulatory cells (Tregs), dendritic cells (DCs) as well as sub-populations of T cells bearing regulatory properties like CD4 + GITR + , CD4 + CD62L + , CD3 + TCR γδ + along with the concentrations of IL-10, TGF β , IL-6 in 66 patients with MM. Subsequently, the influence of therapy on those components of immune system was assessed. Results: The percentage of both myeloid and plasmacytoid DC was lower in MM compared with control group while Treg (CD4 + CD25 high FOXP3 + ) frequencies were significantly higher in MM patients compared with healthy control (6.16% vs 0.05%, respectively). Also, the percentages of CD4 + GITR + , CD4 + CD62L + were increased compared with healthy volunteers. We found that patients with higher percentages of Treg live shorter (median overall survival 21 months vs not-reached, P =0.013). Conclusion: This study identifies several abnormalities of immune system in MM, which only partly could be normalised after successful therapy. The dysfunction of immune system such as decreased antigen presentation along with increased frequencies of suppressive cells and cytokines might facilitate progression of the disease and infectious complications limiting survival of MM patients.