The STAT signaling profile at the single cell level reveals novel insights in the association of FOXP3+ T regulatory cells with recurrent spontaneous abortions before and after lymphocyte immunotherapy

Lamprianidou, Eleftheria; Daniilidis, M.; Kordella, Chryssoula; Zoulia, Emmanouela; Nakou, Evangelia; Gerofotis, A.; Vasilaki, A.; Pantos, George; Kotsianidis, Ιoannis

doi:10.1016/j.clim.2019.108261

Cited by 7 publications

(8 citation statements)

References 43 publications

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“…In addition, a study have shown that MLR‐Bf is IgG3 in nature which is usually absent in women with RPL 42 . Other immune biomarkers used in recent studies that may predict successful pregnancy outcome after LIT include: a. suppressed NK cell activity; 26 b. low levels of IL‐17 and IL‐23; 27 c. high Foxp3+ T regulatory cell (Tregs); 29 d. high plasma levels of IL‐4, IL‐10, and TGFß1; 43 e. low TNF‐α 44 …”

Section: Discussionmentioning

confidence: 99%

“…LIT promotes maternal immune tolerance against the developing fetus by increasing the production of alloantibodies (i.e., APCA, MLR-Bf, or IgG3) and anti-idiotypic antibodies, inhibit natural killer cell activity, 26 restore the imbalance of Th1/Th2 responses by shifting towards a Th2 activity, 28 and induce regulatory T cell (Treg) differentiation. 29 Proposed mechanisms of the therapeutic effect of LIT include production of alloantibodies which act as a protective barrier of embryos against maternal T cell cytotoxicity by masking HLA paternal antigens. 30 Paternal LIT also induces production of anti-T cell receptor (TCR) idiotypic antibodies directed to autologous TCR, thereby inhibiting maternal immune response against the fetus.…”

Section: Efficacy Of Lymphocyte Immunotherapymentioning

confidence: 99%

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Efficacy of lymphocyte immunotherapy in the treatment of recurrent pregnancy loss from alloimmunity: A systematic review and meta‐analysis

Francisco

Tan‐Lim

Jesus

2022

American J Rep Immunol

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Problem The efficacy of lymphocyte immunotherapy (LIT) in the treatment of recurrent pregnancy loss (RPL) from alloimmunity has been debated for years. There is conflicting evidence on the therapeutic role of LIT, since the etiology of most cases of RPL is previously classified as idiopathic. Method of study A systematic search of PubMed and Cochrane databases was done for randomized controlled trials that assessed the efficacy of paternal lymphocyte or third donor LIT among patients with primary or secondary RPL. The primary outcome was live birth rate after LIT. Random‐effect meta‐analysis was conducted using the software RevMan 5.4. Pre‐planned subgroup analyses of source of lymphocytes, timing and frequency of administration, and concentration per immunization dose were conducted. Results Data from eight trials showed a statistically significant benefit of LIT (RR = 1.45, 95% CI 1.05‐2.01). The overall live birth rate is higher in the treatment group (65.6%) compared to placebo or no treatment (45.2%). Subgroup analysis based on source of lymphocytes revealed a trend towards benefit with paternal LIT but with wide confidence interval (RR = 1.34, 95% CI = .84‐2.14). Multiple doses of immunotherapy before pregnancy and low dose (5×106 cells) LIT showed significant benefit. Sensitivity analysis involving studies with a low risk of bias demonstrated significant benefit of increased live birth rate among patients treated with LIT compared to those who received placebo or no treatment (RR = 1.97, 95% CI = 1.53‐2.53). Conclusion LIT demonstrate benefit in improving pregnancy outcome of patients with RPL from alloimmunity.

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Section: Discussionmentioning

confidence: 99%

Section: Efficacy Of Lymphocyte Immunotherapymentioning

confidence: 99%

Efficacy of lymphocyte immunotherapy in the treatment of recurrent pregnancy loss from alloimmunity: A systematic review and meta‐analysis

Francisco

Tan‐Lim

Jesus

2022

American J Rep Immunol

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“…Moreover, PD-1 activation may impair effector T cell proliferation and function while promoting regulatory T cell differentiation and its suppression function [ 7 , 36 ]. Overexpression of dysfunctional Treg cells was reported in women with RSA and preeclampsia [ 37 ]. In addition, in our previous study performed on a similar group of patients, we noticed significantly impaired Th1 cytokine production in RSA patients compared to fertile women, which may suggest immune system exhaustion [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Differences in Immune Checkpoints Expression (TIM-3 and PD-1) on T Cells in Women with Recurrent Miscarriages—Preliminary Studies

Zych

Roszczyk

Kniotek

et al. 2021

JCM

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Background: Immune checkpoints are molecules that regulate the function of immune cells and control inflammation processes. An important role in this regard is played by TIM-3/Gal-9 and PD-1/PDL-1 interactions. Previous research performed in a mouse model of pregnancy loss confirmed that blocking TIM-3 could induce fetal loss. Similarly, the PD-1 molecule maintains protective interactions between the mother’s immune cells and the fetus. The purpose of this study was to assess the expression of these molecules on a range of T lymphocyte subpopulations from non-pregnant women with recurrent spontaneous abortion (RSA) versus healthy fertile women. Methods: PBMCs were isolated by gradient centrifugation of blood obtained from 12 healthy women and 24 women with RSA and immediately stained for flow cytometry analysis. Standard immunophenotyping of PBMC was performed with the antibodies against classical lymphocyte markers: CD3, CD4, CD8, and CD56. Immune checkpoints were investigated using antibodies against PD-1(CD279) and TIM-3(CD366). Results: We found that expression of TIM-3 was significantly decreased on CD8+ T lymphocytes in the RSA group, and expression of PD-1 was upregulated on CD4+ T lymphocytes in the RSA group in comparison to the healthy controls. Conclusions: Considering our findings, therapeutic intervention towards immune checkpoints may be a promising treatment option for recurrent spontaneous abortion.

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“…No data was found in our review regarding conception while receiving ACT for treatment of cancer, highlighting need for additional study Studies of ACT treatment in subjects without cancer suggest it may actually improve pregnancy rates in patients with dysregulation or depletion of their regulatory T cells. In this sub-population, ACT has been shown to improve embryo implantation [ (Heitmann et al, 2017)] and to reduce frequency of spontaneous abortion [ (Lamprianidou et al, 2020)].…”

Section: Conceptionmentioning

confidence: 99%

Targeted cancer treatment and fertility: effect of immunotherapy and small molecule inhibitors on female reproduction

Bussies

Richards

Rotz

et al. 2022

Reproductive BioMedicine Online

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Targeted cancer therapy is rapidly evolving the landscape of personalized health care. Novel approaches to selectively impeding tumor growth carry significant potential to improve survival outcomes, particularly for reproductive-aged patients harboring treatment refractory disease. Current agents fall within two classes, immunotherapy and small molecule inhibitors, which are collectively divided into the following subclasses: monoclonal antibodies, immunomodulators, adoptive cell therapy, treatment vaccines, kinase inhibitors, proteosome inhibitors, metalloproteinase and heat shock protein inhibitors, and promoters of apoptosis. The short-and long-term effects of these therapies on the female reproductive system are not well understood. As a result, clinicians are rendered unable to appropriately counsel women on downstream effects to their fertility. Data-driven consensus recommendations are desperately needed. This review aims to characterize the impact of targeted cancer therapy on the female hypothalamic-pituitary-ovary axis, direct ovarian function, and conception.

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The STAT signaling profile at the single cell level reveals novel insights in the association of FOXP3+ T regulatory cells with recurrent spontaneous abortions before and after lymphocyte immunotherapy

Cited by 7 publications

References 43 publications

Efficacy of lymphocyte immunotherapy in the treatment of recurrent pregnancy loss from alloimmunity: A systematic review and meta‐analysis

Efficacy of lymphocyte immunotherapy in the treatment of recurrent pregnancy loss from alloimmunity: A systematic review and meta‐analysis

Differences in Immune Checkpoints Expression (TIM-3 and PD-1) on T Cells in Women with Recurrent Miscarriages—Preliminary Studies

Targeted cancer treatment and fertility: effect of immunotherapy and small molecule inhibitors on female reproduction

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