IFN-α regulates IL 10 production by CML cells in vitro

Pawelec, Graham; Schlotz, Elke; Rehbein, Arnika

doi:10.1007/s002620050619

Cited by 10 publications

(7 citation statements)

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“…24,25 Generally, CML cells with their characteristic cytogenetic abnormality 28 are recognizable by cells of the immune system, 24,29 Á 31 their escape from immune surveillance may be related to the dysregulated T1-cytokine synthesis 32 sustained by the CML clone. 21 Little is known about the mechanism of action of IFNa treatment in CML, however immunomodulatory effects have been documented.…”

Section: Discussionmentioning

confidence: 99%

“…24,25 Using intracellular cytokine detection, 10 Á 16 we measured T1 cytokine synthesis in freshly isolated CD3 ' cells from CML patients receiving IFN-a therapy or allogeneic BMT. Our data confirmed on a single T-cell level a suppressed T1 cytokine production in untreated chronic-phase CML patients.…”

Section: Discussionmentioning

confidence: 99%

“…20,21 Specifically, chronic-phase CML patients have been shown to produce high levels of the T1-suppressing T2 cytokine IL-10 22 in cultures of their predominantly BCR-ABL 23 -positive PBMC. 24 This has been reversed in vitro in the presence of IFN-a. 24,25 The objective of this study was to analyze the in vivo effects of IFN-a therapy and allogeneic BMT on the intracellular T1 (IFN-g) cytokine production by T cells of patients with CML.…”

Section: Introductionmentioning

confidence: 95%

“…24 This has been reversed in vitro in the presence of IFN-a. 24,25 The objective of this study was to analyze the in vivo effects of IFN-a therapy and allogeneic BMT on the intracellular T1 (IFN-g) cytokine production by T cells of patients with CML.…”

Section: Introductionmentioning

confidence: 95%

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Intracellular cytokine analysis of interferon-? in T cells of patients with chronic myeloid leukemia

Aswald

Lipton

Messner

2002

Cytokines, Cellular & Molecular Therapy

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The role of T cells in eradicating leukemic cells has been well demonstrated for chronic myeloid leukemia (CML). Type 1 (T1) T-cell cytokines play a major role in this antileukemic immune effect. Studies in cancer patients have demonstrated a decreased T1 cytokine production, measured by enzyme-linked immunosorbent assay (ELISA), in cultures of peripheral blood mononuclear cells. This observation of malignancy-related suppressed T1 cytokines also occurs in untreated chronic-phase (CP) CML, raising the question of the influence of different CML treatment regimens on this immunosuppression. Intracellular flow cytometry (ICF) has facilitated the evaluation of cytokines on a single-cell level. This study analyzed T1 (interferon-gamma) cytokine production in purified peripheral blood T cells by ICF, comparing different therapy approaches for CML. Twenty-one newly diagnosed CP CML patients were compared with 24 patients treated with interferon-alpha (IFN-alpha) and to 30 allogeneic bone marrow transplant (BMT) recipients (BCR-ABL negative by reverse-transcriptase polymerase chain reaction, and free of, or having only limited graft-versus-host disease at the time of study). Thirty-seven healthy controls were included. Our results showed a significantly decreased T-cell IFN-gamma synthesis in CP CML patients in relation to healthy controls (P = 0.0007). Treatment with IFN-alpha resulted in a shift from immunosuppression--documented for the group of untreated patients--to immunopotentiation, with an increase of T-cell IFN-gamma production (P = 0.0266). Notably, BMT enhanced IFN-gamma production of T cells to a level not only exceeding untreated patients (P < 0.0001) but also healthy volunteers (P < 0.0001). The observation of T1 cytokine up-regulation with IFN-alpha therapy indicates that enhanced T-cell function may be achievable in patients with CML, even in the absence of an allo-response.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 95%

See 2 more Smart Citations

Intracellular cytokine analysis of interferon-? in T cells of patients with chronic myeloid leukemia

Aswald

Lipton

Messner

2002

Cytokines, Cellular & Molecular Therapy

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“…34 In addition, human CML cells express IL-10 mRNA 35 and produce high levels of IL-10 in vitro. 36 Therefore, the secretion of TGF-␤ and/or IL-10 by leukemic cells may contribute to a reduced maturation status of BCR/ABL-expressing DCs. Second, BCR/ABL activates the signal transducer and activator of transcription (STAT) pathway.…”

Section: Discussionmentioning

confidence: 99%

Defective homing and impaired induction of cytotoxic T cells by BCR/ABL-expressing dendritic cells

Mumprecht

Claus

Schürch

et al. 2009

Blood

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Chronic myelogenous leukemia (CML) is IntroductionChronic myelogenous leukemia (CML) is a malignant clonal myeloproliferative disease. The BCR/ABL fusion protein results from the reciprocal chromosomal translocation t(9;22) forming the Philadelphia chromosome (Ph). BCR/ABL is responsible for the malignant phenotype of leukemic cells in CML and increases cell proliferation, inhibits apoptotic processes, and alters cellular adhesion of myeloid cells. 1,2 CML is characterized by an initial chronic phase with a massive expansion of all stages of the granulocyte cell lineage. Eventually, hematopoietic differentiation becomes arrested and CML progresses to blast crisis with immature blast cells accumulating in the periphery. 1 Several studies have shown that cytotoxic T lymphocytes (CTLs) are involved in the immunosurveillance of CML. BCR/ ABL is a leukemia-specific antigen, and CTLs specific for peptides derived from its sequence could recognize CML cells in vitro and in vivo. 3,4 This suggests that there is efficient intracellular processing and presentation of BCR/ABL-derived peptides by CML cells. In addition, overexpressed self-proteins, such as proteinase-3, Wilms tumor 1 protein, and minor histocompatibility antigens, can act as leukemia-specific antigens for T cells. 5 Dendritic cells (DCs) are professional antigen-presenting cells and are key mediators for the initiation and regulation of both innate and adaptive immune responses. 6 DCs are a heterogeneous population that can be divided into myeloid and plasmacytoid DCs based on their origin, expression of surface markers, and function. 7 As CML mainly affects cells of the myeloid lineage, it is probable that myeloid BCR/ABL-expressing DCs are circulating in CML patients. Indeed, BCR/ABL-expressing DCs could be detected in the peripheral blood of CML patients. 7,8 However, CML patients in chronic phase had reduced numbers of circulating myeloid and plasmacytoid DCs compared with healthy persons. 9,10 Contradictory data regarding the maturation status and function of BCR/ABLexpressing DCs have been published. BCR/ABL-expressing DCs had either a normal maturation status or lower expression of the costimulatory molecules CD80/CD83/CD40 compared with control DCs. 7,8,11,12 In acute myeloid leukemia, the plasmacytoid DCs were immature and could not elicit the proliferation of naive CD4 ϩ T cells. 13 Moreover, in vitro-generated BCR/ABL-expressing DCs have been reported to be defective in antigen processing. 7,11 In contrast, other studies suggested that BCR/ABL-expressing DCs are able to effectively stimulate the proliferation of allogeneic and autologous T cells. 8,14 Similarly, vaccination with autologous, nonirradiated leukemic DCs induced antileukemic T-cell responses in some CML patients. 15 The function of BCR/ABL-expressing DCs in vivo is unknown. Therefore, we analyzed the function of BCR/ABL-expressing DCs in a murine retroviral-induced bone marrow transduction and transplantation model. 16 To study antigen-specific immune responses, we used H8 transgenic...

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Escape Mechanisms in Tumour Immunity

Pawelec¹

2001

Cancer Immunology

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IFN-α regulates IL 10 production by CML cells in vitro

Cited by 10 publications

References 0 publications

Intracellular cytokine analysis of interferon-? in T cells of patients with chronic myeloid leukemia

Intracellular cytokine analysis of interferon-? in T cells of patients with chronic myeloid leukemia

Defective homing and impaired induction of cytotoxic T cells by BCR/ABL-expressing dendritic cells

Escape Mechanisms in Tumour Immunity

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