Functional heterogeneity of circulating T regulatory cell subsets in breast cancer patients

Ostapchuk, Yekaterina O.; Perfilyeva, Yuliya V.; Kustova, Elena; Urazalieva, N. T.; Omarbaeva, Nazgul A.; Talaeva, Shynar G.; Belyaev, Nikolai N.

doi:10.1007/s12282-018-0874-4

Cited by 7 publications

(6 citation statements)

References 53 publications

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“…In line with this, reduced numbers of CD39 + FOXP3 + Tregs were observed in patients affected by multiple sclerosis (MS), indicating that CD39 expression in Tregs is critical in controlling inflammatory autoimmune disorders [ 24 ]. In contrast, circulating levels of CD39 + CD25 + Tregs were elevated in cancer patients [ 47 , 48 ], while their low levels were associated with improved relapse-free survival in melanoma patients [ 49 ]. Accordingly, CD39 + Treg frequency and adenosine-mediated immunosuppression were significantly increased in head and neck patients [ 50 ].…”

Section: Cd39 Expression and Functions In Conventional Cd4 + T Cells And Tregsmentioning

confidence: 99%

CD39 Regulation and Functions in T Cells

Timperi

Barnaba

2021

IJMS

101

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CD39 is an enzyme which is responsible, together with CD73, for a cascade converting adenosine triphosphate into adenosine diphosphate and cyclic adenosine monophosphate, ultimately leading to the release of an immunosuppressive form of adenosine in the tumor microenvironment. Here, we first review the environmental and genetic factors shaping CD39 expression. Second, we report CD39 functions in the T cell compartment, highlighting its role in regulatory T cells, conventional CD4+ T cells and CD8+ T cells. Finally, we compile a list of studies, from preclinical models to clinical trials, which have made essential contributions to the discovery of novel combinatorial approaches in the treatment of cancer.

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Section: Cd39 Expression and Functions In Conventional Cd4 + T Cells And Tregsmentioning

confidence: 99%

CD39 Regulation and Functions in T Cells

Timperi

Barnaba

2021

IJMS

101

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“…Interestingly, another retrospective study analyzed the clinical impact of the expression of CTLA-4 by different cells of the TME in BC showing that the group of patients with high CTLA-4 expression on interstitial lymphocytes and with a low CTLA-4 expression on tumor cells had the best outcomes (DFS and OS) [105]. CTLA-4 expression in both tumor cells and TILs was associated with worse DFS and OS in luminal B HER2− BC [106]. A flow cytometry study investigating the intracellular protein expression of CTLA-4 by BC CD4 + TILs revealed its almost low expression in the luminal versus HER2-positive and TNBC subtypes, as a consequence of their lower baseline immune infiltration [107].…”

Section: Ctla-4: a Key Actor In Cancer Immune Evasionmentioning

confidence: 99%

Luminal Breast Cancer: Risk of Recurrence and Tumor-Associated Immune Suppression

Pellegrino

Hlavatá²,

Migali

et al. 2021

Mol Diagn Ther

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Hormone-receptor positive (HR+) breast cancer (BC) (including the luminal A and the luminal B subtypes) is the most common type of tumor in women diagnosed with early-stage BC (EBC). It represents a highly heterogeneous subgroup that is characterized by different risks of relapse. The aim of this review is to discuss the possible role played by the immune response in predicting this risk, along with the most common clinical and pathological factors and molecular tools that have been developed and are already in use. As opposed to what has previously been observed in the most aggressive human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancer (TNBC) subtypes, a high proportion of tumor-infiltrating lymphocytes (TILs)-reflecting a spontaneous and pre-existing immune response to the tumor-has been linked to a worse prognosis in HR+ EBC. This work provides some immune biological rationale explaining these findings and provides the basics to understand the principal clinical trials that are testing immunotherapy in HR+ (luminal) BC.Antonino Musolino and Cinzia Solinas contributed equally to this work.

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“…Cari et al assessed GITR mRNA expression in 3169 BC patients of all subtypes and found an overexpression in 42% of the cases [31]. Other studies demonstrated that expression is increased in both infiltrating [34] and circulating Tregs of BC patients [35,37]. Interestingly, GITR seems to also be overexpressed in CD4+ T-cells in BC-infiltrated lymph nodes [36] (Table 1).…”

Section: Markers Predominantly Expressed On T-lymphocytesmentioning

confidence: 99%

Beyond PD-1/PD-L1 Inhibition: What the Future Holds for Breast Cancer Immunotherapy

Chrétien

Zerdes

Bergh

et al. 2019

Cancers

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Cancer immunotherapy has altered the management of human malignancies, improving outcomes in an expanding list of diseases. Breast cancer - presumably due to its perceived low immunogenicity - is a late addition to this list. Furthermore, most of the focus has been on the triple negative subtype because of its higher tumor mutational load and lymphocyte-enriched stroma, although emerging data show promise on the other breast cancer subtypes as well. To this point the clinical use of immunotherapy is limited to the inhibition of two immune checkpoints, Programmed Cell Death Protein 1 (PD-1) and Cytotoxic T-lymphocyte-associated Protein 4 (CTLA-4). Consistent with the complexity of the regulation of the tumor – host interactions and their lack of reliance on a single regulatory pathway, combinatory approaches have shown improved efficacy albeit at the cost of increased toxicity. Beyond those two checkpoints though, a large number of co-stimulatory or co-inhibitory molecules play major roles on tumor evasion from immunosurveillance. These molecules likely represent future targets of immunotherapy provided that the promise shown in early data is translated into improved patient survival in randomized trials. The biological role, prognostic and predictive implications regarding breast cancer and early clinical efforts on exploiting these immune-related therapeutic targets are herein reviewed.

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Functional heterogeneity of circulating T regulatory cell subsets in breast cancer patients

Cited by 7 publications

References 53 publications

CD39 Regulation and Functions in T Cells

CD39 Regulation and Functions in T Cells

Luminal Breast Cancer: Risk of Recurrence and Tumor-Associated Immune Suppression

Beyond PD-1/PD-L1 Inhibition: What the Future Holds for Breast Cancer Immunotherapy

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