Mechanisms of tumor immune escape in triple-negative breast cancers (TNBC) with and without mutated BRCA 1

Engel, Jörg B.; Hönig, Arnd; Kapp, Michaela; Hahne, Jens C.; Meyer, Susanne; Dietl, Johannes; Segerer, Sabine

doi:10.1007/s00404-013-2922-9

Cited by 38 publications

(28 citation statements)

References 37 publications

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“…Tregs can inhibit the proliferation and activation of effector T lymphocytes and the secretion of helper T lymphocyte 1 (Th1) cytokines, resulting in the suppression of antitumor immune responses 68. Infiltration of Tregs is suggested to be significantly higher in TNBC than estrogen receptors/progesterone receptors-positive BC 69. Tregs accumulate in BC, indicating that the multiplication of these cells may be the result of both the natural circulatory system and a local trigger 8,30,70.…”

Section: Tumor Microenvironmentmentioning

confidence: 99%

“…Single-dose and combination therapies of the anti-CTLA-4 monoclonal antibody ipilimumab are under evaluation in clinical trials 91. Engel et al demonstrated that expression levels of B7-H1 increased in TNBC but were similar to those found in other BC subgroups 69. However, the elevated expression level of B7-H4 was correlated with the negative status of receptors and the positive state of Her2/neu 92.…”

Section: Tumor Microenvironmentmentioning

confidence: 99%

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Mechanism of immune evasion in breast cancer

Wang¹,

Zhang²,

Song³

et al. 2017

OTT

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Breast cancer (BC) is the most common malignant tumor among women, with high morbidity and mortality. Its onset, development, metastasis, and prognosis vary among individuals due to the interactions between tumors and host immunity. Many diverse mechanisms have been associated with BC, with immune evasion being the most widely studied to date. Tumor cells can escape from the body’s immune response, which targets abnormal components and foreign bodies, using different approaches including modification of surface antigens and modulation of the surrounding environment. In this review, we summarize the mechanisms and factors that impact the immunoediting process and analyze their functions in detail.

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Section: Tumor Microenvironmentmentioning

confidence: 99%

Section: Tumor Microenvironmentmentioning

confidence: 99%

Mechanism of immune evasion in breast cancer

Wang¹,

Zhang²,

Song³

et al. 2017

OTT

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“…Furthermore AKT seems to be able to influence directly the immune resistance of malignant cells e.g. ovarian tumour cells [73,95,[129][130][131]. Comparison of parental and immuneresistant ovarian tumours revealed that AKT is highly activated in the immune-resistant tumours.…”

Section: Resultsmentioning

confidence: 99%

“…Conversely, there is accumulating evidence that the PI3K/AKT/mTOR pathway is involved in the development of several malignant traits of cancer cells as well as their escape from immunity [128]. In some studies the interactions between cancer cells and natural-killer (NK)-cells have been enlightened [73,95,[129][130][131]. Modified FATAL assay was used for determining the killing efficiency of NK-cells in regard to ovarian cancer cell models in-vitro.…”

Section: Role Of Akt Expression Level In Tumour Cells In Regard To Nkmentioning

confidence: 99%

Platinum-resistance and AKT Over-expression in Ovarian Cancer

Hahne¹

2015

Int J Gynecol Clin Pract

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Ovarian cancer is among the most common cause of cancer death and ranks first in the number of deaths each year in the field of gynaecological malignancies. This is due to its late diagnosis and the development of chemoresistance. Platinum derivates, including cisplatinum and carboplatinum in combination with paclitaxel, are the first-line chemotherapeutic agents. Platinum derivates intercalates irreversibly into the DNA and creates inter-and intra-strand DNA cross-links. During cell division, platinum-DNA-adducts block the replication machinery, inducing DNA damage and apoptosis. Nearly all patients respond to first line chemotherapy before it comes later to recurrence of the disease. At time of recurrence, tumours are usually more aggressive, form metastasis in secondary tissues and acquire resistance to conventional chemotherapeutics. Drug resistance is a common problem in tumour therapy not only restricted to ovarian cancer. This is characterized by gene mutations, increased DNA repair, reduced drug efficacy and enhanced drug clearance and detoxification. Up to now the complex molecular mechanism of chemoresistance is not well understood but increasing evidence points towards AKT over-expression and alteration of the PI3K/AKT/mTOR cascade as a central mechanistic reason for this resistance.

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“…To explain the significance of this suppressive effect, we turn to Engel et al 47. who reported that NK cell-induced tumor cell lysis was significantly more pronounced in triple negative breast cancer cells, where estrogen receptor (−) and progesterone receptor (−) did not over-express the HER-2 receptor, compared to ER- positive MCF7 cells47, indicating that MCF7 cells are prone to resist NK cell cancer surveillance. Taken together, it therefore seems highly possible that MCF7 cells escape cancer surveillance via attenuation of NK cells upon the degradation of IFN-γ.…”

Section: Discussionmentioning

confidence: 99%

A-Disintegrin and Metalloproteinase (ADAM) 17 Enzymatically Degrades Interferon-gamma

Kanzaki

Shinohara

Suzuki

et al. 2016

Sci Rep

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Interferon-gamma (IFN-γ) is a pleiotropic cytokine that exerts anti-tumor and anti-osteoclastogenic effects. Although transcriptional and post-transcriptional regulation of IFN-γ is well understood, subsequent modifications of secreted IFN-γ are not fully elucidated. Previous research indicates that some cancer cells escape immune surveillance and metastasize into bone tissue by inducing osteoclastic bone resorption. Peptidases of the a-disintegrin and metalloproteinase (ADAM) family are implicated in cancer cell proliferation and tumor progression. We hypothesized that the ADAM enzymes expressed by cancer cells degrades IFN-γ and attenuates IFN-γ-mediated anti-tumorigenic and anti-osteoclastogenic effects. Recombinant ADAM17 degraded IFN-γ into small fragments. The addition of ADAM17 to the culture supernatant of stimulated mouse splenocytes decreased IFN-γ concentration. However, ADAM17 inhibition in the stimulated mouse T-cells prevented IFN-γ degradation. ADAM17-expressing human breast cancer cell lines MCF-7 and MDA-MB-453 also degraded recombinant IFN-γ, but this was attenuated by ADAM17 inhibition. Degraded IFN-γ lost the functionality including the inhibititory effect on osteoclastogenesis. This is the first study to demonstrate the extracellular proteolytic degradation of IFN-γ by ADAM17. These results suggest that ADAM17-mediated degradation of IFN-γ may block the anti-tumorigenic and anti-osteoclastogenic effects of IFN-γ. ADAM17 inhibition may be useful for the treatment of attenuated cancer immune surveillance and/or bone metastases.

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Mechanisms of tumor immune escape in triple-negative breast cancers (TNBC) with and without mutated BRCA 1

Cited by 38 publications

References 37 publications

Mechanism of immune evasion in breast cancer

Mechanism of immune evasion in breast cancer

Platinum-resistance and AKT Over-expression in Ovarian Cancer

A-Disintegrin and Metalloproteinase (ADAM) 17 Enzymatically Degrades Interferon-gamma

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