Immunosuppressive Tumor Microenvironment in Cervical Cancer Patients

Piersma, Sytse J.

doi:10.1007/s12307-011-0066-7

Cited by 108 publications

(77 citation statements)

References 179 publications

(192 reference statements)

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“…The tumor microenvironment is a complex cellular environment in which the tumor exists; it consists of cancer cells, fibroblasts, immune cells, surrounding blood vessels, cytokines, chemicals and the extracellular matrix (20)(21)(22)(23)(24)(25). The interaction between cancer cells and the tumor microenvironment plays an important role in tumor progression.…”

Section: Discussionmentioning

confidence: 99%

Ovarian cancer stem cells induce the M2 polarization of macrophages through the PPARγ and NF-κB pathways

Deng

Zhang

Liang

et al. 2015

International Journal of Molecular Medicine

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Abstract.Increasing evidence suggests an association between cancer stem cells and the tumor microenvironment. Ovarian cancer stem cell (OCSC) factors can influence the tumor microenvironment and prognosis. However, the effects of OCSCs on macrophage M1/M2 polarization are not yet completely understood. In the present study, we evaluated the effects of OCSCs on macrophage M1/M2 polarization. In addition, we investigated whether the activation of the peroxisome proliferator-activated receptor γ (PPARγ)/nuclear factor-κB (NF-κB) pathway is involved in these effects, thus modulating the M1/M2 differentiation of monocytes into macrophages. The expression levels of markers of the M1 state, such as tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS) and CD86, as well as those of markers of M2 activation, such as mannose receptor (MR), interleukin (IL)-10 and arginase-1 (Arg-1), were measured by RT-qPCR. We found that the OCSCs promoted the M2 polarization of Raw264.7 macrophages by upregulating the expression of MR, IL-10 and Arg-1, while the expression levels of M1 macrophages markers, including TNF-α, iNOS and CD86 were suppressed. In addition, treatment with OCSCs activated PPARγ and suppressed NF-κB in the Raw264.7 cells. Furthermore, the PPARγ, antagonist GW9662, attenuated the promoting effects of OCSCs on the M2 polarization of macrophages. To the best of our knowledge, the findings of the present study, provide the first evidence that OCSCs promote the M2 polarization of macrophages through the PPARγ/ NF-κB pathway.

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Section: Discussionmentioning

confidence: 99%

Ovarian cancer stem cells induce the M2 polarization of macrophages through the PPARγ and NF-κB pathways

Deng

Zhang

Liang

et al. 2015

International Journal of Molecular Medicine

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“…Fourthly, the infected cells express low levels of MHC class I, resulting in impaired CTL function (22). Fifthly, they could induce an accumulation of ineffective CD4 and CD8 T lymphocytes in stage II/III CINs (23).…”

Section: Hpv Infection Regulating the Host Immune Responsementioning

confidence: 99%

“…Firstly, improper activation of the immune response induced by hrHPV infection provides the possibility of the toleration of T cell generation. Secondly, the weakened innate immune function elicited by the infected KCs creates an immunosuppressive microenvironment, promoting HPV-specific Treg expansion (22).…”

Section: Interplay Between Treg Cells and Hrhpv Infection Tregs (Cd4mentioning

confidence: 99%

Effect of human papillomavirus infection on the immune system and its role in the course of cervical cancer

et al. 2015

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Abstract. Human papillomavirus (HPV) is widely known as a cause of cervical intraepithelial neoplasia (CIN) and cervical cancer. The mechanisms involved have been studied by numerous studies. The integration of the virus genome into the host cells results in the abnormal regulation of cell cycle control. HPV can also induce immune evasion of the infected cells, which enable the virus to be undetectable for long periods of time. The induction of immunotolerance of the host's immune system by the persistent infection of HPV is one of the most important mechanisms for cervical lesions. The present review elaborates on the roles of several types of immune cells, such as macrophages and natural killer cells, which are classified as innate immune cells, and dendritic cells (DCs), cluster of differentiation (CD)4 + /CD8 + T cells and regulatory T cells, which are classified as adaptive immune cells. HPV infection could effect the differentiation of these immune cells in a unique way, resulting in the host's immune tolerance to the infection. The immune system modifications induced by HPV infection include tumor-associated macrophage differentiation, a compromised cellular immune response, an abnormal imbalance between type 1 T-helper cells (Th1) and Th2 cells, regulatory T cell infiltration, and downregulated DC activation and maturation. To date, numerous types of preventative vaccines have been created to slow down carcinogenesis. Immune response activation-based therapeutic vaccine is becoming more and more attractive for the treatment of HPV-associated diseases.

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“…The main cause of cervical cancer is continuous infection with human papilloma virus (HPV) (1)(2)(3)(4). Cervical cancer cells rapidly evade the immune system and promote tumor progression by inhibiting antitumor immunity (5)(6)(7)(8). Many reports have demonstrated the expansion of various immunosuppressive cells such as regulatory T cells, tumor-associated macrophages, myeloid-derived suppressor cells (MDSCs), and N2 neutrophils in cervical tumors (7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Circulating and tumor‑infiltrating myeloid‑derived suppressor cells in cervical carcinoma patients

Liu

Guo

et al. 2018

Oncol Lett

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HLA-DR -CD11b + CD33 + MDSCs were then evaluated and the results revealed that they express high CD13 and CD39, and low CD115, CD117, CD124 and programmed cell death ligand 1; they were also devoid of CD14, CD15 and CD66b. MDSCs and T-cells from peripheral blood were sorted by flow cytometry for co-culture experiments. Lin -/low HLA-DR -CD11b + CD33 + MDSCs from patients significantly inhibited the proliferation of CD4 and CD8 T-cells. Furthermore, functional analysis verified that MDSCs from cervical cancer patients could inhibit interleukin-2 and interferon-γ production from T-cells. In addition, the associations between peripheral circulating MDSCs and tumor infiltrating MDSCs, and tumor relapse and metastasis were analyzed. The number of peripheral MDSCs and MDSCs in tumor tissue were observed to be associated with relapse-free survival. Thus, MDSCs in the peripheral blood and tumors of cervical cancer patients have a significant immunosuppressive effect, and are associated with cervical cancer staging and metastasis. These results suggest that targeting MDSCs may increase antitumor immunity and increase the efficacy of cervical cancer therapies.

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Immunosuppressive Tumor Microenvironment in Cervical Cancer Patients

Cited by 108 publications

References 179 publications

Ovarian cancer stem cells induce the M2 polarization of macrophages through the PPARγ and NF-κB pathways

Ovarian cancer stem cells induce the M2 polarization of macrophages through the PPARγ and NF-κB pathways

Effect of human papillomavirus infection on the immune system and its role in the course of cervical cancer

Circulating and tumor‑infiltrating myeloid‑derived suppressor cells in cervical carcinoma patients

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