Monocyte-derived dendritic cells reflect the immune functional status of a chromophobe renal cell carcinoma patient: Could it be a general phenomenon?

Clavijo-Salomon, Maria Alejandra; Ramos, Rodrigo Nalio; Crippa, Alexandre; Pizzo, Célia Regina; Bergami-Santos, Patrícia Cruz; Barbuto, José Alexandre Marzagão

doi:10.1007/s00262-014-1625-9

Cited by 9 publications

(8 citation statements)

References 43 publications

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“…These findings are in accordance with our previous studies, showing that blood monocytes from primary BC give rise to Mo‐DCs that favor Treg responses, partially via TGF‐β . Furthermore, this monocyte skewing phenomenon depends on the tumor burden, since a functional recovery of Mo‐DCs is observed after tumor resection or after immunotherapeutic DC vaccination . Most interestingly, we highlight a heterogeneity among patients, by revealing two distinct transcriptome profiles.…”

Section: Discussionsupporting

confidence: 92%

CD163⁺ tumor‐associated macrophage accumulation in breast cancer patients reflects both local differentiation signals and systemic skewing of monocytes

et al. 2020

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Objectives The accumulation of tumor‐associated macrophages (TAMs) is correlated with poor clinical outcome, but the mechanisms governing their differentiation from circulating monocytes remain unclear in humans. Methods Using multicolor flow cytometry, we evaluated TAMs phenotype in 93 breast cancer (BC) patients. Furthermore, monocytes from healthy donors were cultured in the presence of supernatants from dilacerated primary tumors to investigate their differentiation into macrophages (MΦ) in vitro. Additionally, we used transcriptomic analysis to evaluate BC patients’ blood monocytes profiles. Results We observed that high intra‐tumor CD163‐expressing TAM density is predictive of reduced survival in BC patients. In vitro, M‐CSF, TGF‐β and VEGF from primary tumor supernatants skewed the differentiation of healthy donor blood monocytes towards CD163highCD86lowIL‐10high M2‐like MΦ that strongly suppressed CD4+ T‐cell expansion via PD‐L1 and IL‐10. In addition, blood monocytes from about 40% of BC patients displayed an altered response to in vitro stimulation, being refractory to type‐1 MΦ (M1‐MΦ) differentiation and secreting higher amounts of immunosuppressive, metastatic‐related and angiogenic cytokines. Aside from showing that monocyte transcriptome is significantly altered by the presence of BC, we also demonstrated an overall metabolic de‐activation in refractory monocytes of BC patients. In contrast, monocytes from sensitive BC patients undergoing normal M1‐MΦ differentiation showed up‐regulation of IFN‐response genes and had no signs of metabolic alteration. Conclusion Altogether, our results suggest that systemic factors skew BC patient blood monocytes towards a pro‐metastatic profile, resulting in the accumulation of further polarised CD163high TAMs resembling type‐2 MΦ (M2‐MΦ) in the local BC microenvironment. These data indicate that monitoring circulating monocytes in BC patients may provide an indication of early systemic alterations induced by cancer and, thus, be instrumental in the development of improved personalised immunotherapeutic interventions.

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Section: Discussionsupporting

confidence: 92%

CD163⁺ tumor‐associated macrophage accumulation in breast cancer patients reflects both local differentiation signals and systemic skewing of monocytes

et al. 2020

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“…However, the surface phenotype of DCs is not always predictive of their function ( 19 ); so, we evaluated the ability of iDCs, MC-iDC, and TW-iDCs to stimulate allogeneic CD3 + T cells. On the one hand, TW-iDCs were not more efficient than control iDCs as T cell stimulators (Figure 4 A), despite their increased levels of HLA-DR and CD86 expression.…”

Section: Resultsmentioning

confidence: 99%

“…Though the phenotype of MC-iDC suggested a poor T-cell stimulating ability, the surface phenotype of DCs is not always predictive of their function ( 19 ). So, in order to assess if the phenotype of MC-iDC corresponded to a decreased stimulatory function, we tested their ability to induce the proliferation of allogeneic T cells, and it was, in fact, poor.…”

Section: Discussionmentioning

confidence: 99%

Tolerogenic IDO+ Dendritic Cells Are Induced by PD-1-Expressing Mast Cells

et al. 2016

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Mast cells (MCs) are tissue resident cells, rich in inflammatory mediators, involved in allergic reactions, and with an increasingly recognized role in immunomodulation. Dendritic cells (DCs), on the other hand, are central to the determination of immune response patterns, being highly efficient antigen-presenting cells that respond promptly to changes in their microenvironment. Here, we show that direct cell contact between immature monocyte-derived DCs (iDCs) and MC bends DCs toward tolerance induction. DCs that had direct contact with MC (MC-iDC) decreased HLA-DR but increased PD-L1 expression and stimulated regulatory T lymphocytes, which expresses FoxP3+, secrete TGF-β and IL-10, and suppress the proliferation of mitogen-stimulated naïve T lymphocytes. Furthermore, MC-iDC expressed higher levels of indoleamine-2,3-deoxigenase (IDO), a phenomenon that was blocked by treatment of MC with anti-PD-1 or by the treatment of DCs with anti-PD-L1 or anti-PD-L2, but not by blocking of H1 and H2 histamine receptors on DCs. Contact with MC also increased phosphorylated STAT-3 levels in iDCs. When a STAT-3 inhibitor, JSI-124, was added to the DCs before contact with MC, the MC-iDC recovered their ability to induce allogeneic T cell proliferation and did not increase their IDO expression.

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“…In our present case, the histiocytic area was mainly composed of CD163+CD206+ M2-polarized macrophages and CD205+ dendritic cells, both of which could express PD-L1 by the stimulation of cancer stromal factors to induce an immunosuppressive microenvironment at the tumor sites [ 11 , 14 ]. Notably, since the expression of PD-L1 on TAMs was associated with high levels of CD4+ and CD8+ tumor-infiltrating lymphocytes [ 15 ], the PD-L1-expressing TAMs and dendritic cells might suggest favorable prognostic factors in patients with PEM.…”

Section: Discussionmentioning

confidence: 99%

Pigmented Epithelioid Melanocytoma (Animal Types of Melanoma) on the Nose

Ohuchi¹,

Fujimura²,

Kambayashi³

et al. 2018

Case Rep Oncol

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Pigmented epithelioid melanocytoma (PEM), also known as an animal-type melanoma, is a distinctive group of melanocytic tumors with a more favorable prognosis than conventional melanoma. Since tumor-associated macrophages (TAMs) extend in the premetastatic lymph nodes in several cancers, we hypothesized that the lower rate of lymph node metastasis in PEM might be correlated with the phenotypes of TAMs. Therefore, in this report, we further investigate the subpopulation of TAMs in PEM, revealing that the main population of TAMs in histiocytic lesion is CD163+CD206+PD-L1+ M2-polarized macrophages. In addition, since the PD-L1-expressing CD205+ dendritic cells are also detected in histiocytic lesions, the PD-L1-expressing TAMs and dendritic cells might suggest favorable prognostic factors in patients with PEM.

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Monocyte-derived dendritic cells reflect the immune functional status of a chromophobe renal cell carcinoma patient: Could it be a general phenomenon?

Cited by 9 publications

References 43 publications

CD163⁺ tumor‐associated macrophage accumulation in breast cancer patients reflects both local differentiation signals and systemic skewing of monocytes

CD163⁺ tumor‐associated macrophage accumulation in breast cancer patients reflects both local differentiation signals and systemic skewing of monocytes

Tolerogenic IDO+ Dendritic Cells Are Induced by PD-1-Expressing Mast Cells

Pigmented Epithelioid Melanocytoma (Animal Types of Melanoma) on the Nose

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Monocyte-derived dendritic cells reflect the immune functional status of a chromophobe renal cell carcinoma patient: Could it be a general phenomenon?

Cited by 9 publications

References 43 publications

CD163+ tumor‐associated macrophage accumulation in breast cancer patients reflects both local differentiation signals and systemic skewing of monocytes

CD163+ tumor‐associated macrophage accumulation in breast cancer patients reflects both local differentiation signals and systemic skewing of monocytes

Tolerogenic IDO+ Dendritic Cells Are Induced by PD-1-Expressing Mast Cells

Pigmented Epithelioid Melanocytoma (Animal Types of Melanoma) on the Nose

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CD163⁺ tumor‐associated macrophage accumulation in breast cancer patients reflects both local differentiation signals and systemic skewing of monocytes

CD163⁺ tumor‐associated macrophage accumulation in breast cancer patients reflects both local differentiation signals and systemic skewing of monocytes