Monocyte Subsets and Their Role in Tumor Progression

Doseff, Andrea I.; Parihar, Arti

doi:10.5772/32615

Cited by 6 publications

(7 citation statements)

References 106 publications

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“…Among such obstacles, the TME and its cellular components appear to play the most crucial role ( 15 , 29 ). In particular, monocytes are recruited from the circulation to the tumor site and are known to express PD-L1 that, when bound to PD-1 expressed on physiological T cells, may suppress T cell proliferation and cytotoxic activity toward cancer cells ( 19 , 28 , 29 ). Nevertheless, it remains to be clarified if such immunosuppression occurs with engineered TCR T cells.…”

Section: Discussionmentioning

confidence: 99%

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Characterizing the Role of Monocytes in T Cell Cancer Immunotherapy Using a 3D Microfluidic Model

et al. 2018

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In the hepatitis B virus (HBV)-related hepatocellular carcinoma tumor microenvironment (TME), monocytes reportedly impede natural T cell functions via PD-L1/PD-1 signaling. However, it remains unclear if T cell receptor-redirected T cells (TCR T cells) are similarly inhibited. Hence, we developed a 3D intrahepatic TME microfluidic model to investigate the immunosuppressive potential of monocytes toward HBV-specific TCR T cells and the role of PD-L1/PD-1 signaling. Interestingly, in our 3D static microfluidic model, we observed that monocytes suppressed only retrovirally transduced (Tdx) TCR T cell cytotoxicity toward cancer cells via PD-L1/PD-1, while mRNA electroporated (EP) TCR T cell cytotoxicity was not affected by the presence of monocytes. Importantly, when co-cultured in 2D, both Tdx and EP TCR T cell cytotoxicity toward cancer cells were not suppressed by monocytes, suggesting our 3D model as a superior tool compared to standard 2D assays for predicting TCR T cell efficacy in a preclinical setting, which can thus be used to improve current immunotherapy strategies.

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Section: Discussionmentioning

confidence: 99%

“…Monocytes/macrophages constitute a major component of the tumor stroma and are known to importantly modulate effector T cell activity via PD-L1 ( 19 , 28 , 29 ). Notably, in response to TME-specific signals, monocytes can acquire unique phenotypes and functions to become tumor-associated macrophages ( 30 – 32 ).…”

Section: Introductionmentioning

confidence: 99%

Characterizing the Role of Monocytes in T Cell Cancer Immunotherapy Using a 3D Microfluidic Model

et al. 2018

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“…The second subpopulation of CD16-positive monocytes was found to be characterized by a very low expression of the CD14 molecule and a high expression of CD16 (CD14 low /CD16 ++ ) [ 2 , 10 ]. In the following years, numerous attempts were made to understand the phenotypic and functional heterogeneity of each of the three discovered monocyte subpopulations [ 3 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Reduced Percentage of CD14dimCD16+SLAN+ Monocytes Producing TNF and IL-12 as an Immunological Sign of CLL Progression

Kowalska

Zarobkiewicz

Tomczak

et al. 2022

IJMS

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Monocytes are one of the least studied immune cells with a potentially important role in the pathogenesis of chronic lymphocytic leukemia (CLL). Nevertheless, data regarding the role of subpopulations of monocytes in the CLL microenvironment are still limited. For the very first time, this study presents an assessment of monocyte subsets divided according to SLAN and CD16 expression in CLL patients. The study involved 70 freshly diagnosed CLL patients and 35 healthy donors. Using flow cytometry, monocyte subpopulations were assessed among PBMCs. CD14+ monocytes can be divided into: “classical” (CD14+CD16−SLAN−), “intermediate” (CD14+CD16+SLAN−) and “non-classical” (CD14dimCD16+SLAN+). In our study, we noted an increased percentage of non-classical monocytes with intracellular expression of TNF and IL-12. On the other hand, among the intermediate monocytes, a significantly higher percentage of cells synthesizing anti-inflammatory IL-10 was detected. The percentage of CD14dimCD16+SLAN+ monocytes producing TNF and IL-12 decreased with the stage of CLL and inversely correlated with the expression of the prognostic factors ZAP-70 and CD38. Moreover, the percentage of CD14dimCD16+SLAN+ monocytes producing TNF and IL-12 was lower in CLL patients requiring treatment. This may indicate the beneficial effect of non-classical monocytes on the anti-tumor response.

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“…It contains several types of inflammatory cells including MOs and macrophages. MO cells represent a heterogeneous population derived from myeloid lineages [ 6 ] that are recruited from the bloodstream to the tumor site through the paracrine action of cytokines and chemokines released by breast cancer cells [ 7 ]. Previous reports suggested that infiltration of MOs into the breast tumor microenvironments, in response to paracrine stimulation, correlates with poor prognosis and promotion of tumor growth, invasion and metastasis [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Metformin partially reverses the inhibitory effect of co-culture with ER-/PR-/HER2+ breast cancer cells on biomarkers of monocyte antitumor activity

et al. 2020

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Background Immune activities of monocytes (MOs) can be altered within the microenvironment of solid malignancies, including breast cancer. Metformin (1,1-dimethylbiguanide hydrochloride, MET), has been shown to decrease tumor cell proliferation, but its effects have yet to be explored with respect to MOs (monocytes) activity during their crosstalk with breast cancer cells. Here, we investigated the effects of MET on overall phenotypic functional activities, including cellular immunometabolism and protective redox signaling based-biomarkers, intracellular free calcium ions ( if Ca 2+ ), phagocytosis and co-operative cytokines (IFN-γ and IL-10) of autologous MOs before and during their interplay with primary ER - /PR - /HER2 + breast cancer cells. Methods Human primary breast cancer cells were either cultured alone or co-cultured with autologous MOs before treatment with MET. Results MET downregulated breast cancer cell proliferation and phagocytosis, while having no significant effect on the ratio of phosphorylated Akt (p-Akt) to total Akt. Additionally, we observed that, in the absence of MET treatment, the levels of lactate dehydrogenase (LDH)-based cytotoxicity, catalase, if Ca 2+ , IL-10 and arginase activity were significantly reduced in co-cultures compared to levels in MOs cultured alone whereas levels of inducible nitric oxide synthase (iNOS) activity were significantly increased. In contrast, MET treatment reduced the effects measured in co-culture on the levels of LDH-based cytotoxicity, arginase activity, catalase, if Ca 2+ , and IFN-γ. MET also induced upregulation of both iNOS and arginase in MO cells, although the increase did not reach significant difference for iNOS activity. Moreover, MET induced a robust increase of superoxide dismutase (SOD) activity in MOs, but not in MOs co-cultured with breast cancer cells. Furthermore, MET markedly upregulated the levels of IFN-γ production and downregulated those of IL-10 in isolated MOs, while inducing a slight opposing up-regulation of IL-10 production in co-cultures. Conclusions Our results show that the biomarkers of phenotypic functional activities of MOs are modified after co-culturing with primary human breast cancer cells. Treatment of co-cultures with MET resulted in increased release of antitumor cytokine IFN-γ and if Ca 2+ , and increased cell necrosis during breast cancer cells-MOs crosstalk.

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Monocyte Subsets and Their Role in Tumor Progression

Cited by 6 publications

References 106 publications

Characterizing the Role of Monocytes in T Cell Cancer Immunotherapy Using a 3D Microfluidic Model

Characterizing the Role of Monocytes in T Cell Cancer Immunotherapy Using a 3D Microfluidic Model

Reduced Percentage of CD14dimCD16+SLAN+ Monocytes Producing TNF and IL-12 as an Immunological Sign of CLL Progression

Metformin partially reverses the inhibitory effect of co-culture with ER-/PR-/HER2+ breast cancer cells on biomarkers of monocyte antitumor activity

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