Ability of recombinant interferon γ in vitro to restore the defective polymorphonuclear-cell-but not lymphocyte-mediated cytotoxic activities in patients with myelodysplastic syndromes

CD163+ tumor-associated macrophages (TAMs) play an important role in the progression of cancer. However, the significance of CD163+ TAMs in malignant pleural effusion (MPE) is still unclear. The aim of this study is to evaluate the prognostic value of CD163+ TAMs in MPE, and the regulatory effect of an immune adjuvant (pseudomonas aeruginosa - mannose-sensitive hemagglutinin, PA-MSHA, which is used for MPE treatment in clinic) on CD163+ TAMs in MPE. Here, we found that the percentage of CD163+ TAMs in MPE was significantly higher than that in non-malignant pleural effusion (P<0.001). More importantly, CD163+ TAMs in MPE patients were an independent prognostic factor for progression-free survival. M2-related cytokines were highly expressed in MPE-derived CD163+ TAMs than in MPE-derived CD163− macrophages (P<0.05). CD163+ TAMs frequency in MPE patients was obviously reduced after PA-MSHA treatment in clinic (P<0.05). After treatment with PA-MSHA, M2 macrophages were re-educated to M1 macrophages in vitro. TLR4 blocking antibody inhibited M2 macrophages polarization to M1 macrophages induced by PA-MSHA. These findings highlight that accumulation of CD163+ TAMs in MPE caused by lung cancer is closely correlated with poor prognosis. CD163+ TAMs are associated with therapeutic effect in MPE. PA-MSHA re-educates CD163+ TAMs to M1 macrophages through TLR4-mediated pathway in MPE.

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Immunological Findings in Patients with Myelodysplastic Syndrome

Felzmann

Gisslinger²,

Ludwig

1994

Leukemia & Lymphoma

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Activation of monocytes and granulocytes in vitro by cytokines, in vivo administration of cytokines, as well as in vivo cytokine production due to infectious and inflammatory diseases causes changes of the surface expression density of certain membrane molecules. In recent studies we attempted to determine the feasibility of using flow cytometric immunophenotyping as a tool to develop a sensitive parameter for detecting infections at an early stage of disease when clinical parameters are still negative. Since infections are an important factor determining the clinical course of myelodysplastic syndromes (MDS), early detection of infection might be beneficial for these immunocompromised patients. We indeed found activation-associated immunophenotypic changes of cell surface antigens on monocytes and granulocytes of clinically infection free MDS patients suggesting enhanced immune activity in these patients, most likely due to latent or beginning infections. In particular, analyses of the expression density of receptors for IgG (Fc gamma Rs), complement receptors, and certain activation-associated surface molecules such as the CD67 and the M5 molecule seem to be of clinical relevance. We will also discuss findings concerning changes of cytokine levels and functional alterations of immunologic parameters in MDS patients.

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Ability of recombinant interferon γ in vitro to restore the defective polymorphonuclear-cell-but not lymphocyte-mediated cytotoxic activities in patients with myelodysplastic syndromes

Cited by 3 publications

References 26 publications

Effects of Pseudomonas aeruginosa mannose-sensitive hemagglutinin (PA-MSHA) pretreatment on septic rats

Effects of Pseudomonas aeruginosa mannose-sensitive hemagglutinin (PA-MSHA) pretreatment on septic rats

CD163+ tumor-associated macrophage is a prognostic biomarker and is associated with therapeutic effect on malignant pleural effusion of lung cancer patients

Immunological Findings in Patients with Myelodysplastic Syndrome

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