Immune Checkpoint Molecules in Reproductive Immunology

Mikó, Éva; Meggyes, Mátyás; Doba, Katalin; Barakonyi, Alíz; Szereday, László

doi:10.3389/fimmu.2019.00846

Cited by 76 publications

(68 citation statements)

References 110 publications

(179 reference statements)

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“…These data suggest that the same competitive bindings observed in EC are in place also during pregnancy. The increased presence of CTLA4 and its ligand at the decidua is positively correlated with Th2 cytokines secretion and negatively with Th1 cytokines production (114), pointing out the CTLA4 remarkable role on local immune-suppression effect. CTLA-4 is also involved in pregnancy complications, such as recurrent pregnancy loss and preeclampsia (115,116), highlighting the hypothesis to use them as immune disruption challenging models, to be translated in EC cancer.…”

Section: Ctla-4mentioning

confidence: 95%

Endometrial Cancer Immune Escape Mechanisms: Let Us Learn From the Fetal–Maternal Interface

Bruno¹,

Corrado

Baci

et al. 2020

Front. Oncol.

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The immune escape mechanisms at the base of tumor progression in endometrial cancer mimic immune tolerance mechanisms occurring at the maternal-fetal interface. The biological and immunological processes behind the maternal-fetal interface are finely tuned in time and space during embryo implantation and subsequent pregnancy stages; conversely, those behind cancer progression are often aberrant. The environment composition at the maternal-fetal interface parallels the pro-tumor microenvironment identified in many cancers, pointing to the possibility for the use of the maternal-fetal interface as a model to depict immune therapeutic targets in cancer. The framework of cancer environment signatures involved in immune adaptations, precisely timed in cancer progression, could reveal a specific "immune clock" in endometrial cancer, which might guide clinicians in patient risk class assessment, diagnostic workup, management, surgical and therapeutic approach, and surveillance strategies. Here, we review studies approaching this hypothesis, focusing on what is known so far about oncofetal similarities in immunity with the idea to individualize personalized immunotherapy targets, through the downregulation of the immune escape stage or the reactivation of the pro-inflammatory processes suppressed by the tumor.

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Section: Ctla-4mentioning

confidence: 95%

Endometrial Cancer Immune Escape Mechanisms: Let Us Learn From the Fetal–Maternal Interface

Bruno¹,

Corrado

Baci

et al. 2020

Front. Oncol.

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“…Immune checkpoint molecules, such as TIM‐3, PD‐1, and CTLA‐4, are negative regulators of immune responses occurring on the surface of several immune cells . After ligand (galectin‐9, PD‐L1/PD‐L2, CD80/CD86) binding, these regulators are capable of transducing inhibitory signals leading to decreased immunoactivation …”

Section: Introductionmentioning

confidence: 99%

“…TIM‐3 and PD‐1 were shown to be expressed by many types of immune cells, including Th1, Th17, NK and NKT cells, γ/δ T cells, Tregs, and also on antigen‐presenting immune cells . The ligand of TIM‐3 receptor is galectin‐9 (Gal‐9), a β‐galactose binding protein.…”

Section: Introductionmentioning

confidence: 99%

“…Both in mice and humans, binding of TIM‐3 to its ligand Gal‐9 leads to the apoptosis of Th1 and Th17 cells and induces active immunotolerance . Known ligands of PD‐1 include PD‐L1, which can be found on several immune cells (resting T cells, B cells, dendritic cells, macrophages), in various tissues, like placenta, heart, and spleen and by Sertoli and peritubular cells in the testis of mice . In contrast to that, PD‐L2 expression is limited to dendritic cells and macrophages .…”

Section: Introductionmentioning

confidence: 99%

“…Immune checkpoint regulators are thought to actively participate in the immune defense of infections, prevention of autoimmunity, immune reaction during transplantation, tumor immune evasion, and maternal immune tolerance during pregnancy …”

Section: Introductionmentioning

confidence: 99%

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Phenotypic characterization of testicular immune cells expressing immune checkpoint molecules in wild‐type and pituitary adenylate cyclase‐activating polypeptide‐deficient mice

Meggyes

Lajko

Fülöp

et al. 2019

American J Rep Immunol

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Problem Pituitary adenylate cyclase‐activating polypeptide (PACAP) is a neuropeptide having several regulatory functions in the nervous system and in peripheral organs including those of the reproductive system. PACAP‐deficient male mice have several morphological, biochemical, behavioral defects and show disturbed signaling in spermatogenesis affecting fertility in PACAP KO mice. Reproductive functions such as fertility, mating, and maternal behaviors have been widely investigated, but no immune analyses are available regarding the testicular immune‐privileged environment in male PACAP‐deficient mice. Method of Study We performed detailed immunophenotyping of testicular immune cells and investigated the expression of TIM‐3 and PD‐1 Immune checkpoint molecules of immune cells together with the detection of galectin‐9 and perforin. We investigated the percentage of numerous immune cell populations in the testis of wild‐type and PACAP‐deficient mice. Results We demonstrated a significant increase in the frequency of testicular CD8+ T cells together with the decrease in Treg cell number obtained from PACAP KO mice compared with wild‐type mice. Investigating Immune checkpoint receptors, only PD‐1 showed a significantly decreased expression in CD8+ T cells in PACAP KO mice compared with wild‐type suggesting an impaired PD‐1/PD‐L1 pathway. Regarding TIM‐3 expression, we did not find any significant difference between the investigated groups. Conclusion We hypothesize that these local changes may result in an immune activation with disturbed testicular immunoregulation in PACAP KO mice; however, determining the exact function requires further investigations. Our data further support the view that besides a systemic immune tolerance, localized active immunosuppression is involved in the regulation of testicular immune privilege.

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Engineered Cell Membrane‐Derived Nanoparticles in Immune Modulation

et al. 2021

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Immune modulation is one of the most effective approaches in the therapy of complex diseases, including public health emergency. However, most immune therapeutics such as drugs, vaccines, and cellular therapy suffer from the limitations of poor efficacy and adverse side effects. Fortunately, cell membrane-derived nanoparticles (CMDNs) have superior compatibility with other therapeutics and offer new opportunities to push the limits of current treatments in immune modulation. As the interface between cells and outer surroundings, cell membrane contains components which instruct intercellular communication and the plasticity of cytomembrane has significantly potentiated CMDNs to leverage our immune system. Therefore, cell membranes employed in immunomodulatory CMDNs have gradually shifted from natural to engineered. In this review, unique properties of immunomodulatory CMDNs and engineering strategies of emerging CMDNs for immune modulation, with an emphasis on the design logic are summarized. Further, this review points out some pressing problems to be solved during clinical translation and put forward some suggestions on the prospect of immunoregulatory CMDNs. It is anticipated that this review can provide new insights on the design of immunoregulatory CMDNs and expand their potentiation in the precise control of the dysregulated immune system.

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Immune Checkpoint Molecules in Reproductive Immunology

Cited by 76 publications

References 110 publications

Endometrial Cancer Immune Escape Mechanisms: Let Us Learn From the Fetal–Maternal Interface

Endometrial Cancer Immune Escape Mechanisms: Let Us Learn From the Fetal–Maternal Interface

Phenotypic characterization of testicular immune cells expressing immune checkpoint molecules in wild‐type and pituitary adenylate cyclase‐activating polypeptide‐deficient mice

Engineered Cell Membrane‐Derived Nanoparticles in Immune Modulation

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