Myeloid Cells

Monocytes have been categorized in three main subpopulations based on CD14 and CD16 surface expression. Classical monocytes express the CD14(++)CD16(-) CCR2(+) phenotype and migrate to inflammatory sites by quickly responding to CCL2 signaling. Here, we identified and characterized the expansion of a novel monocyte subset during HIV and SIV infection, which were undistinguishable from classical monocytes, based on CD14 and CD16 expression, but expressed significantly lower surface CCR2. Transcriptome analysis of sorted cells demonstrated that the CCR2(low/neg) cells are a distinct subpopulation and express lower levels of inflammatory cytokines and activation markers than their CCR2(high) counterparts. They exhibited impaired phagocytosis and greatly diminished chemotaxis in response to CCL2 and CCL7. In addition, these monocytes are refractory to SIV infection and suppress CD8(+) T cell proliferation in vitro. These cells express higher levels of STAT3 and NOS2, suggesting a phenot...

A major barrier for cancer immunotherapy is the presence of suppressive cell populations in patients with cancer, such as myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM), which contribute to the immunosuppressive microenvironment that promotes tumor growth and metastasis. Tasquinimod is a novel antitumor agent that is currently at an advanced stage of clinical development for treatment of castration-resistant prostate cancer. A target of tasquinimod is the inflammatory protein S100A9, which has been demonstrated to affect the accumulation and function of tumor-suppressive myeloid cells. Here, we report that tasquinimod provided a significant enhancement to the antitumor effects of two different immunotherapeutics in mouse models of cancer: a tumor vaccine (SurVaxM) for prostate cancer and a tumor-targeted superantigen (TTS) for melanoma. In the combination strategies, tasquinimod inhibited distinct MDSC populations and TAMs of the M2-polarized phenotyp...

Background: The antitumor immune response in patients with B-cell NHL plays an important role in determining clinical outcome. We have previously shown that an increased absolute monocyte count in the peripheral blood of lymphoma patients is associated with a poor prognosis. Furthermore, we have identified a population of CD14+HLADRlow monocytes in NHL patients that are immunosuppressive. The goal of this study was to further define the phenotype of suppressive monocytes in lymphoma patients and to identify the conditions that promote their expansion. Methods: Peripheral blood specimens were obtained from patients with newly diagnosed, untreated B-cell NHL (n=20) and 20 matched controls; and the phenotype of the monocyte fraction was analyzed by 10-color flow cytometry. Monocytes from an additional 15 healthy controls were polarized to express a phenotype similar to that seen in lymphoma patients. Serum from 361 lymphoma patients and 337 matched controls were used to confirm differences in cytokine production. Results: The number of monocytes in the peripheral blood of NHL patients was increased compared to controls (p=0.024), due in part to an increase in CD14+CD16- HLADRlow monocytes that also expressed CD32 and CD163, and were positive for IL-10. Increased levels of IL-10 were found in the serum of lymphoma patients (median: 27.5ng/ml; 14.5-53.4) when compared to controls (median: 16.4ng/ml; 8.8-26, p=0.001). Monocytes from healthy donors were then polarized with GMCSF+/-LPS and IFNg or MCSF+/-IL-4 to attempt to mimic the phenotype seen in lymphoma patients. Monocytes treated with MCSF+/-IL-4 developed a similar phenotype to monocytes from lymphoma patients and were CD14+CD16-IL10+, however they remained HLADR+. When MCSF- or GMCSF-treated monocytes were co-cultured with T-cells, MCSF-treated monocytes suppressed T-cell cytokine secretion and induced FoxP3 expression. Conclusions: CD14+CD16-HLADRlow monocytes in NHL patients express immunosuppressive ligands, secrete IL-10 and suppress T-cell function. They may represent a therapeutic target in lymphoma patients.

The aim of this study was to evaluate lineage-specific chimerism reconstitution after reduced-intensity allogeneic stem cell transplantation (RIST) using a combination of fludarabine (30 mg/m2 for 6 days) and busulfan (4 mg/kg for 2 days). We prospectively enrolled 8 consecutive patients with hematologic malignancies who were not candidates for conventional transplantation because of either high age or organ dysfunction. Host-donor chimerism was evaluated using polymerase chain reaction-based amplification of a polymorphic short tandem repeat region. All of our patients achieved engraftment within a median of 11 days after transplantation. On day 30, full donor myeloid cell chimerism (>90%) was achieved in 7 patients whereas full donor T-cell chimerism was achieved in only one patient. Thus, in contrast to other reported results, full donor chimerism was achieved earlier in the myeloid lineage than the T-cell lineage. On day 60, however, T-cell chimerism caught up with myeloid ch...

M. tuberculosis and M. leprae are considered to be prototypical intracellular pathogens that have evolved strategies to enable growth in the intracellular phagosomes. In contrast, we show that lysosomes rapidly fuse with the virulent M. tuberculosis-and M. leprae-containing ...

The role of angiogenesis in the growth of lymphomas and survival of patients with leukemias and other hematological malignancies has become evident since 1994. Angiogenic factors, such as vascular endothelial growth factor and its receptors together with other tumor microenvironment components, including myelo-monocytic cell, mast cells, endothelial progenitor cells, and circulating endothelial cells, have been shown to be important in the progression and maintenance of lymphoproliferative disorders. In this review article, we present an overview of the literature focusing on the relationship between angiogenesis and disease progression and the recent advantages in the antiangiogenic treatment in human non-Hodgkin lymphomas.

Flow cytometry is nowadays the first-line method for immunophenotypic identification of blast cells but is not so usual in limited-resources countries. We have investigated on the usefulness of this tool in Abidjan, Côte d'Ivoire. Bone marrow sample from 13 patients with acute leukemia identified by cytology and cytochemical analysis was immunophenotyped by using monoclonal antibodies directed to: T lymphoid cells (CD3, CD5, CD7); B lymphoid cells (CD10, CD19, CD20, CD22, HLA-DR) and myeloid cells (CD13, CD33). Immunophenotyping allowed us to confirm the diagnosis of 6 de novo acute leukemias (2 acute myeloid leukaemias, 4 acute lymphoid leukemias) and 7 acute leukaemias resulting from chronic myeloid leukaemias. Immunophenotyping also characterizes the atypical/aberrant lineage essential for the prognosis: 2 biphenotypic acute leukemias (myeloid/lymphoid T) were identified. Our results suggest that flow cytometry may be a useful additional tool to identify the specific leukemic...

Cell-cell interactions mediated by cell surface receptor-ligand pairs in the immune system are often of low affinity and transient in nature. To begin to study these weak interactions, it is desirable to devise a generally applicable method for screening for and enriching cells expressing low-affinity ligands for specific cell surface receptors. We describe here an experimental strategy that uses a multivalent form of protein as a probe to identify and characterize cognate ligand(s) of myeloid cell surface receptors. Recombinant fusion proteins containing the receptor protein fragment of interest fused to a truncated Fc domain and a unique biotinylation signal are produced, biotinylated, and coupled to (strep)avidin-coated fluorescent or paramagnetic microspheres. These multivalent microparticle probes are then used to screen or capture cells expressing the cognate cellular ligand(s).