| 1. |
- Allaoui, Roni, et al.
(författare)
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Cancer-associated fibroblast-secreted CXCL16 attracts monocytes to promote stroma activation in triple-negative breast cancers
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Triple-negative (TN) breast cancers (ER â ' PR â ' HER2 â ') are highly metastatic and associated with poor prognosis. Within this subtype, invasive, stroma-rich tumours with infiltration of inflammatory cells are even more aggressive. The effect of myeloid cells on reactive stroma formation in TN breast cancer is largely unknown. Here, we show that primary human monocytes have a survival advantage, proliferate in vivo and develop into immunosuppressive myeloid cells expressing the myeloid-derived suppressor cell marker S100A9 only in a TN breast cancer environment. This results in activation of cancer-associated fibroblasts and expression of CXCL16, which we show to be a monocyte chemoattractant. We propose that this migratory feedback loop amplifies the formation of a reactive stroma, contributing to the aggressive phenotype of TN breast tumours. These insights could help select more suitable therapies targeting the stromal component of these tumours, and could aid prediction of drug resistance.
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| 2. |
- Allaoui, Roni, et al.
(författare)
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Infiltration of γδ T cells, IL-17 + T cells and FoxP3 + T cells in human breast cancer
- 2017
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Ingår i: Cancer Biomarkers. - 1574-0153. ; 20:4, s. 395-409
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Tumor-infiltrating lymphocytes (TILs) have a strong prognostic value in various forms of cancers. These data often refer to use of the pan-T cell marker CD3, or the cytotoxic T lymphocyte marker CD8α. However, T cells are a heterogeneous group of cells with a wide array of effector mechanisms ranging from immunosuppression to cytotoxicity. OBJECTIVE: In this study we have investigated the prognostic effects of some unconventional T cell subtypes in breast cancer; γδ T cells, IL-17+ T cells and FoxP3+ T cells (Tregs) in relation to the conventional CD3 and CD8α T cell markers. METHODS: This was done using immunohistochemistry on a human breast cancer tissue microarray consisting of 498 consecutive cases of primary breast cancer. RESULTS: Infiltration of γδ T cells and T cell infiltration in general (CD3), correlated with a good prognosis, while Treg infiltration with a worse. Infiltration of γδ T cells was associated with a significantly improved clinical outcome in all breast cancer subtypes except triple negative tumors. Only infiltration of either CD3+ or CD8α+ cells was independently associated with better prognosis for all breast cancer patients. CONCLUSIONS: This study sheds further light on the prognostic impact of various T cell subtypes in breast cancer.
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| 3. |
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| 4. |
- Bergenfelz, Caroline, et al.
(författare)
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S100A9 expressed in ER(-)PgR(-) breast cancers induces inflammatory cytokines and is associated with an impaired overall survival.
- 2015
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 113:8, s. 1234-1243
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer is the most common cancer form among women today. Depending on hormone receptor status, breast cancers are divided into different subtypes with vastly varying prognosis. S100A9 is a calcium-binding protein that is associated with inflammation and expressed not only in myeloid cells but also in some tumours. The role for S100A9 in the malignant cells is not well characterised; however, previous studies have shown that the protein could have important immune-modulating properties.
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| 5. |
- Gunnarsdóttir, Frida Björk, et al.
(författare)
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Inflammatory macrophage derived TNFα downregulates estrogen receptor α via FOXO3a inactivation in human breast cancer cells
- 2020
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Ingår i: Experimental Cell Research. - : Elsevier BV. - 0014-4827. ; 390:1
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Tidskriftsartikel (refereegranskat)abstract
- Patients with estrogen receptor α positive (ERα+) breast cancer can respond to endocrine therapy, but treatment resistance is common and associated with downregulation of ERα expression in the dormant residual cells. Here we show, using long-term NSG xenograft models of human breast cancer and primary human monocytes, in vitro primary cell cultures and tumors from breast cancer patients, that macrophage derived tumor necrosis factor alpha (TNFα) downregulates ERα in breast cancer cells via inactivation of the transcription factor Forkhead box O transcription factor 3a (FOXO3a). Moreover, presence of tumor associated macrophages in the primary tumor of breast cancer patients, was associated with ERα negativity, and with worse prognosis in patients with ERα+ tumors. We propose that pro-inflammatory macrophages, despite being tumoricidal, may have direct effects on tumor progression and endocrine resistance in breast cancer patients. Our findings suggest that TNFα antagonists should be evaluated for treatment of ERα+ breast cancer.
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| 6. |
- Janols, Helena, et al.
(författare)
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A high frequency of MDSCs in sepsis patients, with the granulocytic subtype dominating in gram-positive cases.
- 2014
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Ingår i: Journal of Leukocyte Biology. - 1938-3673. ; 96:5, s. 685-693
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Tidskriftsartikel (refereegranskat)abstract
- The causative microorganisms dictate the type of MDSC generated in sepsis patients, and a large proportion of PMN-MDSCs in gram-positive sepsis includes immunosuppressive myeloid blasts. MDSCs constitute a heterogeneous population of immature myeloid cells that potently suppress immune responses. They were identified originally in cancer patients and have since been reported to occur also in chronic inflammation, autoimmunity, and even bacterial infections. Human MDSCs are commonly divided into Mo-MDSCs and granulocytic (PMN-MDSCs) subtypes. To what extent the bona fide cancer MDSCs are representative of the proposed MDSCs found in other diseases is not well known. PMN-MDSCs have been found previously to be enriched among LDGs in density gradient-centrifuged blood. In this study, we analyzed potential MDSCs in sepsis patients with different causative microorganisms, using total peripheral blood compared with density gradient-centrifuged blood. We found a high frequency of typical CD14(+)HLA-DR(low) Mo-MDSCs in all sepsis patients, whereas the typical PMN-MDSCs, as well as a prominent CD14(low) PMN-MDSC-like population, appeared preferentially in gram-positive cases. The CD14(low) PMN-MDSC variant was demonstrated to suppress T cell proliferation in vitro via a ROS-dependent mechanism, to display an increased IL-10:TNF-α ratio, and to present with signs of immaturity: blast morphology and low cytokine levels. We conclude that a spectrum of cells with MDSC features is enriched in sepsis and that the microbial origin of sepsis contributes to the substantial interindividual patient variation in the MDSC pattern.
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| 7. |
- Krawczyk, Krzysztof M., et al.
(författare)
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Papillary renal cell carcinoma-derived chemerin, IL-8, and CXCL16 promote monocyte recruitment and differentiation into foam-cell macrophages
- 2017
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Ingår i: Laboratory Investigation. - : Elsevier BV. - 0023-6837. ; 97:11, s. 1296-1305
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Tidskriftsartikel (refereegranskat)abstract
- Papillary renal cell carcinoma (pRCC) is the second most common type of renal cell carcinoma. The only curative treatment available for pRCC is radical surgery. If the disease becomes widespread, neither chemo- nor radiotherapy will have therapeutic effect, hence further research on pRCC is of utmost importance. Histologically, pRCC is characterized by a papillary growth pattern with focal aggregation of macrophages of the foam cell phenotype. In other forms of cancer, a clear role for tumor-associated macrophages during cancer growth and progression has been shown. Although the presence of foamy macrophages is a histological hallmark of pRCC tumors, little is known regarding their role in pRCC biology. In order to study the interaction between pRCC tumor and myeloid cells, we established primary cultures from pRCC tissue. We show that human pRCC cells secrete the chemokines IL-8, CXCL16, and chemerin, and that these factors attract primary human monocytes in vitro. RNAseq data from The Cancer Genome Atlas confirmed a high expression of these factors in pRCC tissue. Conditioned medium from pRCC cultures induced a shift in human monocytes toward the M2 macrophage phenotype. In extended cultures, these macrophages became enlarged and loaded with lipids, adopting the foam cell morphology found in pRCC tissue. These results show for the first time that pRCC primary tumor cells secrete factors that attract and differentiate monocytes into anti-inflammatory tumor-associated macrophages with foam cell histology.
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| 8. |
- Källberg, Eva, et al.
(författare)
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AIRE is expressed in breast cancer TANs and TAMs to regulate the extrinsic apoptotic pathway and inflammation
- 2024
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Ingår i: Journal of Leukocyte Biology. - 1938-3673. ; 115:4, s. 664-678
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune regulator (AIRE) is a transcriptional regulator expressed in the thymus and necessary for maintaining immunological self-tolerance. Extra-thymic AIRE expression is rare and a role for AIRE in tumor-associated innate immune cells has not yet been established. In this study we show that AIRE is expressed in human pro-tumor neutrophils. In breast cancer, AIRE was primarily located to tumor associated neutrophils (TANs), and to a lesser extent to tumor associated macrophages (TAMs) and tumor cells. Expression of AIRE in TAN/TAMs, but not in cancer cells, was associated with an adverse prognosis. We show that the functional role for AIRE in neutrophils and macrophages is to regulate expression of immune mediators and the extrinsic apoptotic pathway involving the Fas/TNFR death receptors and Cathepsin G. We here propose that the role for AIRE in TAN/TAMs in breast tumors is to regulate cell death and inflammation, thus promoting tumor progression.
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| 9. |
- Mehmeti, Meliha, et al.
(författare)
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Expression of functional toll like receptor 4 in estrogen receptor/progesterone receptor-negative breast cancer.
- 2015
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Toll-like receptors (TLRs) are a family of pattern recognition receptors that are expressed on cells of the innate immune system. The ligands can be pathogen derived (pathogen associated molecular patterns; PAMPs) or endogenous (damage associated molecular patters; DAMPs) that when bound induces activation of nuclear factor kappa B (NF-κB) and transcription of pro-inflammatory genes. TLRs have also been discovered in various malignant cell types, but with unknown function.
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