Interaction between Treg cells and tumor-associated macrophages in the tumor microenvironment of epithelial ovarian cancer

Zhu, Qinyi; Wu, Xiaoli; Wu, Yuwei; Wang, Xipeng

doi:10.3892/or.2016.5136

Cited by 55 publications

(47 citation statements)

References 28 publications

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“…Treg cells are not only responsible for the evasion of cancer cells from immune surveillance, but also cooperate with other immune cells, including TAMs, which are predominantly from M2 subgroups [29,30]. These subgroups are responsible for the secretion of TGF-beta and Il-10 that support the differentiation of Treg cells [31]. TAM may also interact with Treg cells in the tumor microenvironment, producing exosomes, such as miRNAs [4].…”

Section: Discussionmentioning

confidence: 99%

Analysis of the treg cell population in the peripheral blood of ovarian cancer patients in relation to the long-term outcomes

Dutsch-Wicherek

Szubert²,

Dziobek

et al. 2019

Ginekol Pol

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Objectives: There is growing evidence that Treg cell infiltration into the cancer nest is associated with poor prognosis. However, the Treg cell population in the peripheral blood may change when a different type of anticancer therapy is applied. Since Treg cells may support tumor growth by enhancing the suppressive profile of the cancer microenvironment, the assessment of Treg cells can bring to light important information regarding prognosis. Thus we decided to analyze the Treg cell population in the peripheral blood in relation to long-term outcomes in the group of patients with ovarian cancer. Material and methods:The 80 patients included in the study were treated surgically followed by chemiotherapy for ovarian cancer between October 2010 through May 2011.The peripheral blood samples from the patients were collected directly prior to chemotherapy. Information on any patients who died was retrieved from the database of the Cuiavia-Pomerania Regional Office of the National Health System of Poland. CD4+CD25+FOXP3+ lymphocytes T were assed by flow cytometry. We have analyzed the long term outcomes of treatment regarding to the level of Treg cells in peripheral blood. Results:We found that patients with serous adenocarcinomas had significantly higher Treg levels compared to those patients with non-serous types. Patients who had a higher percentage of Treg cells within the CD4+ cell population prior to the beginning of the treatment had worse long-term outcomes from the applied therapy. Conclusions:The assessment of Treg levels prior to the start of chemotherapy is clinically useful and may predict overall survival in ovarian cancer patients.

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Section: Discussionmentioning

confidence: 99%

Analysis of the treg cell population in the peripheral blood of ovarian cancer patients in relation to the long-term outcomes

Dutsch-Wicherek

Szubert²,

Dziobek

et al. 2019

Ginekol Pol

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“…High frequency of Tregs in OvCa specimens was associated with significantly shorter overall survival time. Mechanistic studies showed that IL‐10 secreted by TAMs increases the frequency of Tregs through activation of Foxp3 during T‐cell differentiation . Consistently, Treg percentages were significantly higher in patients with OvCa than with benign ovarian tumors (BOT) or healthy controls.…”

Section: Introductionmentioning

confidence: 77%

“…Mechanistic studies showed that IL-10 secreted by TAMs increases the frequency of Tregs through activation of Foxp3 during T-cell differentiation. 82 Consistently, Treg percentages were significantly higher in patients with OvCa than with benign ovarian tumors (BOT) or healthy controls. Higher percentages of Tregs were found in patients with stage III/IV than stage I/ II OvCa.…”

Section: Tumor-associated Lymphocytes (Tils) Comprise T-cells and Rementioning

confidence: 83%

“…Tregs are divided into naturally occurring thymus‐generated Tregs with a phenotype of CD4 + CD25 + FOXP3 + and the adaptive Tr1 Treg and Th3 Tregs with variable CD25 expression. The frequency of Treg cells and TAMs was significantly higher in the OvCa patients than those with benign ovarian tumors . High frequency of Tregs in OvCa specimens was associated with significantly shorter overall survival time.…”

Section: Introductionmentioning

confidence: 82%

“…The frequency of Treg cells and TAMs was significantly higher in the OvCa patients than those with benign ovarian tumors. 82 High frequency of Tregs in OvCa specimens was associated with significantly shorter overall survival time. Mechanistic studies showed that IL-10 secreted by TAMs increases the frequency of Tregs through activation of Foxp3 during T-cell differentiation.…”

Section: Tumor-associated Lymphocytes (Tils) Comprise T-cells and Rementioning

confidence: 94%

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Role of tumor microenvironment in the pathobiology of ovarian cancer: Insights and therapeutic opportunities

et al. 2018

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Ovarian cancer is the fifth most common cancer affecting women and at present, stands as the most lethal gynecologic malignancy. The poor disease outcome is due to the nonspecific symptoms and the lack of effective treatment at advanced stages. Thus, it is of utmost importance to understand ovarian carcinoma through several lenses and to dissect the role that the unique peritoneal tumor microenvironment plays in ovarian cancer progression and metastasis. This review seeks to highlight several determinants of this unique tumor microenvironment, their influence on disease outcome and ongoing clinical trials targeting these determinants.

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Crucial role of glucosylceramide synthase in the regulation of stem cell‐like cancer cells in B16F10 murine melanoma

Ghosh

Juin

Majumdar

et al. 2021

Molecular Carcinogenesis

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Cancer stem cells render a complex cascade of events that facilitates highly invasive melanoma malignancy. Interplay between immunocytes and cancer stem cells within tumor microenvironment with the participation of sphingolipid signaling mediators skews the immune evasion strategies toward metastatic neoplasm. In this context, we aimed to explore the functional aspect of glucosylceramide synthase (GCS), a key enzyme of sphingolipid biosynthesis in the maintenance of melanoma stem cell-like cancer cells (CSCs). Our findings demonstrated that tumor hypoxia was responsible for elevated GCS expression in melanoma, which was correlated with substantially increased melanoma CSCs. Moreover, hypoxia-induced TGF-β from TAMs and Tregs promoted GCS induction in B16F10 murine melanoma CSCs via PKCα signaling and facilitated the expansion of melanoma CSCs. Interestingly, GCS ablation hindered the immunosuppressiveness of TAMs and Tregs. Therefore, our study for the first time demonstrated a novel paracrine pathway of melanoma CSC maintenance and tumorigenicity, exploiting the bidirectional signaling with immunocytes. Furthermore, our study showed that the combinatorial immunotherapy involving immunomodulators like Mw and DTA-1 repressed CSC pool affecting GCS functions in advanced-stage B16F10 murine melanoma tumor. Moreover, GCS inhibition sensitized conventional chemotherapeutic drug-resistant melanoma CSCs to the genotoxic drugs paving the way toward selective melanoma treatment. Better therapeutic efficacy with inhibition of GCS and CSC depletion suggests a crucial role of GCS in melanoma treatment, therefore, implying its application concerning clinical challenges of chemotherapy resistance leading to prolonged survival.

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Interaction between Treg cells and tumor-associated macrophages in the tumor microenvironment of epithelial ovarian cancer

Cited by 55 publications

References 28 publications

Analysis of the treg cell population in the peripheral blood of ovarian cancer patients in relation to the long-term outcomes

Analysis of the treg cell population in the peripheral blood of ovarian cancer patients in relation to the long-term outcomes

Role of tumor microenvironment in the pathobiology of ovarian cancer: Insights and therapeutic opportunities

Crucial role of glucosylceramide synthase in the regulation of stem cell‐like cancer cells in B16F10 murine melanoma

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