Myeloid cell diversification and complexity: an old concept with new turns in oncology

Chioda, Mariacristina; Peranzoni, Elisa; Desantis, Giacomo; Papalini, Francesca; Falisi, Erika; Solito, Samantha; Mandruzzato, Susanna; Bronte, Vincenzo

doi:10.1007/s10555-011-9268-1

Cited by 37 publications

(36 citation statements)

References 140 publications

(205 reference statements)

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“…In order to avoid the potentially confounding effects of treatment with either inhaled or systemic corticosteroids, we limited this study to mild asthmatic subjects who were receiving no corticosteroid medications, and to subjects with moderately severe COPD who also had not received either inhaled or systemic steroids in the six weeks prior to entering our study. Comparing normal subjects and subjects with mild asthma or moderately severe COPD, we show differences between the study groups in the cell surface markers displayed on subsets of MDRC 3, 37, 41, 42 and in the free radicals produced by them. Additional studies will be needed to test whether there are significant differences in the numbers and functional activities of MDRC subsets in the airways of subjects with mild asthma compared to moderate and severe asthma, and how treatment with inhaled or systemic corticosteroids may alter the MDRC repertoire.…”

Section: Discussionmentioning

confidence: 84%

Subsets of airway myeloid-derived regulatory cells distinguish mild asthma from chronic obstructive pulmonary disease

Deshane

Redden

Zeng

et al. 2015

Journal of Allergy and Clinical Immunology

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BACKGROUND Subsets of myeloid-derived regulatory cells (MDRC), phenotypically similar to myeloid-derived suppressor cells found in cancer, have recently been appreciated as critical regulators of airway inflammation in mouse models of asthma. OBJECTIVE We test the hypothesis that subsets of airway MDRC contribute differentially to the inflammatory milieu in human asthma and chronic obstructive pulmonary disease (COPD). METHODS We used BAL to identify and characterize human airway MDRC from 10 normal, 9 mild asthmatic and 8 COPD subjects, none treated with inhaled or systemic corticosteroids. We defined subsets of airway MDRC by flow cytometry, the molecular mediators they produce and their abilities to regulate proliferation of polyclonally activated autologous T-lymphocytes. RESULTS We found substantial differences in the functional potential of MDRC subsets in normal, asthmatic and COPD subjects, with these differences regulated by the nitrosative and oxidative free radicals and cytokines they produced. Nitric oxide-producing MDRC suppressed and superoxide-producing MDRC enhanced proliferation of polyclonally activated autologous CD4 T-cells. HLA-DR+CD11+CD11c+CD163− superoxide-producing MDRC, which stimulated proliferation of autologous T-cells, comprised a high fraction of MDRC in airways of subjects with mild asthma or COPD, but not normals. CD11b+CD14+CD16−HLA-DR− nitric oxide-producing MDRC, which suppressed T-cell proliferation, were present in high numbers in airways of subjects with mild asthma, but not subjects with COPD or normals. CONCLUSION Subsets of airway MDRC conclusively discriminate mild asthmatics, subjects with COPD and normal subjects from each other. The distinctive activities of these MDRC in asthma and COPD may provide novel targets for new therapeutics in these common disorders.

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Section: Discussionmentioning

confidence: 84%

Subsets of airway myeloid-derived regulatory cells distinguish mild asthma from chronic obstructive pulmonary disease

Deshane

Redden

Zeng

et al. 2015

Journal of Allergy and Clinical Immunology

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“…However, the general concern is that adoptive transfer of T cells will be ineffective because of immune suppression by the host. Numerous studies have shown that cells of the myeloid lineage can have substantial immunosuppressive activity (for review see (2)). The CD11b + cells that suppress T cells in cancer include local tumor-associated macrophages (TAM) and systemic Gr1 + cells of the monocytic or granulocytic lineages, also referred to as myeloid-derived suppressor cells (MDSC) (3).…”

Section: Introductionmentioning

confidence: 99%

Adoptively Transferred Immune T Cells Eradicate Established Tumors despite Cancer-Induced Immune Suppression

Arina

Schreiber

Binder

et al. 2014

The Journal of Immunology

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Myeloid-derived CD11b+Gr1+ suppressor cells (MDSC) and tumor-associated macrophages (TAM) are considered a major obstacle for effective adoptive T cell therapy. Myeloid cells suppress naive T cell proliferation ex vivo and can prevent the generation of T cell responses in vivo. We find, however, that immune T cells adoptively transferred eradicate well-established tumors in the presence of MDSC and TAM which are strongly immunosuppressive ex vivo. These MDSC and TAM were comparable in levels and immunosuppression among different tumor models. Longitudinal microscopy of tumors in vivo revealed that after T cell transfer tumor vasculature and cancer cells disappeared simultaneously. During T-cell mediated tumor destruction, the tumor stroma contained abundant myeloid cells (mainly TAM) that retained their suppressive properties. Preimmunized but not naive mice resisted immune suppression caused by an unrelated tumor-burden supporting the idea that in vivo, myeloid immunosuppressive cells can suppress naive but not memory T cell responses.

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“…Specifically, tumors are able to generate TAMs, dysregulated or tolerogenic DCs (Tol-DCs) and MDSCs, which can contribute to the immunosuppression seen during cancer (Chioda et al, 2011; Huang et al, 2011; Mantovani et al, 2009; Pollard, 2004). Tumor-derived soluble factors (TDSFs), such as cytokines, growth factors or tumor exosomes secreted by tumor cells can have direct effects on myeloid cells (Finn, 2008; Mantovani et al, 2008; Pollard, 2004; Zou, 2005).…”

Section: Introductionmentioning

confidence: 99%

Suppression of canine myeloid cells by soluble factors from cultured canine tumor cells

Wasserman¹,

Diese²,

VanGundy³

et al. 2012

Veterinary Immunology and Immunopathology

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Background Cancer profoundly affects immunity and causes immunosuppression that contributes to tumor escape, metastases and resistance to therapy. The mechanisms by which cancer cells influence immune cells are not fully known but both innate and adaptive immune cells can be altered by cancer. Myeloid cells are innate immune cells that comprise the mononuclear phagocytic system (MPS) and include monocytes, macrophages, dendritic cells (DCs) and their progenitors. Myeloid cells play important roles in both the promotion and regulation of immune responses. Dysregulated myeloid cells are increasingly being recognized as contributing to cancer-related immunosuppression. This study investigated whether soluble factors produced by canine tumor cells inhibited canine myeloid cell function. Methods These studies investigated the utility of using the canine DH82 cell line for assessment of canine myeloid responses to tumor-derived soluble factors (TDSFs). Phenotypic comparisons to canine bone marrow-derived DCs (BM-DCs) and bone marrow-derived macrophages (BM-MΦs) were performed and expression of myeloid cell markers CD11b, CD11c, CD80, and major histocompatibility complex (MHC) class II were evaluated by flow cytometry. Phenotypic and functional changes of DC populations were then determined following exposure to tumor-conditioned media (TCM) from canine osteosarcoma, melanoma and mammary carcinoma cell lines. Results We found that the canine BM-DCs and the DH82 cell line shared similar CD11b, CD11c and MHC II expression and morphologic characteristics that were distinct from canine BM-MΦs. Myeloid cells exposed to TDSFs showed decreased expression of MHC class II and CD80, had reduced phagocytic activity and suppressed the proliferation of responder immune cells. Conclusion These results show that soluble factors secreted from canine tumor cells suppress the activation and function of canine myeloid cells. Our results suggest that, similar to humans, dysregulated myeloid cells may contribute to immunosuppression in dogs with cancer.

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Myeloid cell diversification and complexity: an old concept with new turns in oncology

Cited by 37 publications

References 140 publications

Subsets of airway myeloid-derived regulatory cells distinguish mild asthma from chronic obstructive pulmonary disease

Subsets of airway myeloid-derived regulatory cells distinguish mild asthma from chronic obstructive pulmonary disease

Adoptively Transferred Immune T Cells Eradicate Established Tumors despite Cancer-Induced Immune Suppression

Suppression of canine myeloid cells by soluble factors from cultured canine tumor cells

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