High Frequency of T Reg Cells in CLL is Decreased by Thalidomide

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[2108] High Frequency of T Regulatory Cells in Patients with B-Cell

Chronic Lymphocytic Leukemia (B-CLL) Is Decreased by Thalidomide and

Fludarabine Treatment. Session Type: Poster Session, Board #286-II

Krzysztof Giannopoulos, Schmitt, ina Wlasiuk, Malgorzata

Kowal, Monika Podhorecka, Jacek Rolinski, Dmoszynska Clinical

Immunology, Medical University of Lublin, Lublin, Poland; Hemato

Oncology, Medical University of Lublin, Lublin, Poland; Internal

Medicine III, University of Ulm, Ulm, Germany

Background and Aims: Immunotherapy might represent a novel

therapeutical option for patients with B-cell chronic lymphocytic

leukemia (B-CLL). Especially patients with limited tumor burden are

usually regarded as suitable group for immunotherapy. However the

existence of several molecular changes resulting in immunosuppression

was reported even in patients with early stages of disease. In

current study we assessed the expression of CD25 and FOXP3 in CD4

cells from patients with B-CLL. We also evaluated the influence of

immunomodulatory treatment using thalidomide and fludarabine on T

regulatory cells (Tregs) population in patients with B-CLL.

Methods: Forty B-CLL patients (mean age: 64,1 , range: 37 - 79) were

evaluated for the expression of CD4, CD25 as well as specific

transcription factor FOXP-3 (Forkhead box protein P3) by FACS

analysis. Results were compared to those obtained in healthy

volunteers (HV). Mixed lymphocyte cell culture with synthetic peptide

(MLPC) that correspond to epitope of tumor associated antigen RHAMM ,

survivin or fibromodulin were perform to assess antitumor T cell

reactivity in B-CLL patients.

Results: We identified subpopulation of CD4+CD25highFOXP3+ T cells

that phenotypically corresponds to Tregs in B-CLL patients. Increased

levels of Tregs were observed in B-CLL patients. Significantly higher

percentages of Tregs were noted in advanced stages of disease, 11.04%

in stage 0-II vs 17.84% in stage III and IV according to Rai

classification (Fig1a).

No correlation between Tregs percentages and ZAP-70 status was shown,

though interestingly a tendency to higher percentages in ZAP-70

negative patients was observed 9.9% vs. 13.2%. In 9 CLL patients

treated with thalidomide and fludarabine significant reduction of

absolute number of circulating Tregs after thalidomide was observed

(Fig.1b), in 7 this decrease was enhanced by addition of fludarabine

to the treatment. First results from MLPC showed no correlation

between specific T cell responses against TAA and presence of T

regulatory cells.

Conclusion: Increased number of Treg cells in patients with B-CLL

suggests that immunosuppression is present in B-CLL patients not only

in advanced but also in early stages of disease, and that T cell

mediated immune rejection of CLL cell might be hampered by Treg cell.

Effective treatment of B-CLL with novel schema combining

immunomodulatory drug thalidomide with fludarabine seems to be

effective in getting rid of excess of circulating Tregs.