Immunologic Checkpoint Molecules and Their Role in Reproduction and Cancer

A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Hematology and Immunology".

Deadline for manuscript submissions: closed (10 June 2022) | Viewed by 11286

Special Issue Editor

Special Issue Information

Dear Colleagues,

Immune checkpoint molecules, such as FasL/Fas, TIM-3/Gal-9, and PD-1/PD-L1, are regulators of immune responses of the fetus that prevent its rejection by the maternal immune system.

On the other hand, checkpoint inhibitors are among the most promising therapeutic approaches for the treatment of a variety of cancers, leading to strong immune responses against tumor cells by blocking PD1/PD-L1 or TIM-3/Gal-9. Immunostaining for PD-L1 has already become a valid predictive biomarker and is routinely analyzed in several types of cancer. Several reports have demonstrated that PD1/PD-L1 or TIM-3/Gal-9 inhibitors might be useful for cancer treatment approaches. However, there exist difficulties because of the tumor types studied; whether PD1/PD-L1 or TIM-3/Gal-9 expression is a good prognostic marker remains controversial.

In addition, interaction between the receptor Fas (CD95) and Fas Ligand (FasL, CD178) can efficiently induce apoptosis and is critical for the maintenance of immunological tolerance. In invasive carcinomas, the expression of Fas and FasL may be inversely related. During pregnancy, trophoblast and decidual FasL-expressing cells induce apoptosis in the Fas-bearing activated T-cells of the maternal–fetal interface, thus minimizing the risk of embryo rejection during implantation and early development.

Therefore, this Special Issue deals with a variety immunologic checkpoint molecules and their functions in reproductive immunology and cancer biology.

Prof. Dr. Udo Jeschke
Guest Editor

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Keywords

  • FasL/Fas
  • TIM-3/Gal-9
  • PD-1/PD-L1
  • reproductive immunology
  • cancer biology

Published Papers (4 papers)

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Research

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11 pages, 5671 KiB  
Article
PD-L1 Expression in Different Segments and Histological Types of Ovarian Cancer According to Lymphocytic Infiltrate
by Ljubiša Jovanović, Radmila Janković, Andja Ćirković, Milena Jović, Tijana Janjić, Slaviša Djuričić and Svetlana Milenković
Medicina 2021, 57(12), 1309; https://doi.org/10.3390/medicina57121309 - 29 Nov 2021
Cited by 6 | Viewed by 1944
Abstract
Background and Objectives: Ovarian cancer is the leading cause of death among gynecological tumors. PD-1/PD-L1 immunoregulatory mechanism is activated in ovarian cancers. Lymphocyte infiltration is a significant factor that affects its expression. We analyzed the correlation between localization of lymphocytic infiltrate and [...] Read more.
Background and Objectives: Ovarian cancer is the leading cause of death among gynecological tumors. PD-1/PD-L1 immunoregulatory mechanism is activated in ovarian cancers. Lymphocyte infiltration is a significant factor that affects its expression. We analyzed the correlation between localization of lymphocytic infiltrate and PD-L1 expression in epithelial ovarian tumors. Materials and Methods: PD-L1 expression was analyzed in 328 subjects, 122 with epithelial ovarian carcinoma, 42 with atypical proliferative tumor, and 164 with benign epithelial ovarian tumor. Expression in central and invasive tumor parts in epithelial ovarian carcinoma was combined with the most pronounced lymphocyte reaction. Immunohistochemical analysis was performed using the tissue microarray and correlated with a set of histopathology parameters. Results: PD-L1 expression was most prominent in epithelial ovarian carcinoma with different levels of expression observed between invasive and central tumor segments. A high level of PD-L1 expression on tumor cells was more frequently present in the invasive than in the central tumor parts (p < 0.001) only in high-grade serous ovarian carcinoma (HGSC). There was no significant correlation between peritumoral lymphocytic infiltrate and PD-L1 expression regardless of tumor segment. In the central tumor parts of HGSC, there was a correlation of intratumoral lymphocytic infiltrate with a higher level of PD-L1 expression (p = 0.003). Conclusions: The most prominent PD-L1 expression was observed in the invasive tumor parts of HGSC. Only the central parts of the HGSC exhibited significant PD-L1 expression in association with considerable intratumoral lymphocytic infiltrate. Full article
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Review

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12 pages, 3886 KiB  
Review
The Role of the Immune Checkpoint Molecules PD-1/PD-L1 and TIM-3/Gal-9 in the Pathogenesis of Preeclampsia—A Narrative Review
by Johanna Mittelberger, Marina Seefried, Manuela Franitza, Fabian Garrido, Nina Ditsch, Udo Jeschke and Christian Dannecker
Medicina 2022, 58(2), 157; https://doi.org/10.3390/medicina58020157 - 20 Jan 2022
Cited by 10 | Viewed by 2929
Abstract
Preeclampsia is a pregnancy-specific disease which is characterized by abnormal placentation, endothelial dysfunction, and systemic inflammation. Several studies have shown that the maternal immune system, which is crucial for maintaining the pregnancy by ensuring maternal-fetal-tolerance, is disrupted in preeclamptic patients. Besides different immune [...] Read more.
Preeclampsia is a pregnancy-specific disease which is characterized by abnormal placentation, endothelial dysfunction, and systemic inflammation. Several studies have shown that the maternal immune system, which is crucial for maintaining the pregnancy by ensuring maternal-fetal-tolerance, is disrupted in preeclamptic patients. Besides different immune cells, immune checkpoint molecules such as the programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1 system) and the T-cell immunoglobulin and mucin domain-containing protein 3/Galectin-9 (TIM-3/Gal-9 system) are key players in upholding the balance between pro-inflammatory and anti-inflammatory signals. Therefore, a clear understanding about the role of these immune checkpoint molecules in preeclampsia is essential. This review discusses the role of these two immune checkpoint systems in pregnancy and their alterations in preeclampsia. Full article
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10 pages, 314 KiB  
Review
Function of Follicular Cytokines: Roles Played during Maturation, Development and Implantation of Embryo
by Rafał Adamczak, Natalia Ukleja-Sokołowska, Kinga Lis and Mariusz Dubiel
Medicina 2021, 57(11), 1251; https://doi.org/10.3390/medicina57111251 - 16 Nov 2021
Cited by 17 | Viewed by 2577
Abstract
A balance within the immune system is necessary for the proper development of ovarian follicles. Numerous cytokines were detected in follicular fluid, the role of which in reproductive physiology seems crucial. They influence the development and maturation of the follicle, ovulation, and corpus [...] Read more.
A balance within the immune system is necessary for the proper development of ovarian follicles. Numerous cytokines were detected in follicular fluid, the role of which in reproductive physiology seems crucial. They influence the development and maturation of the follicle, ovulation, and corpus luteum formation, as well as embryo implantation and maintenance of pregnancy. The analysis of follicular fluid requires its collection by puncturing of the ovary, which is usually executed in connection with various gynaecological procedures. When interpreting such test results, clinical indications for a given procedure and the method of patient preparation should be taken into account. This review revealed the results of currently available studies on the concentration of pro-inflammatory cytokines in follicular fluid in various forms of infertility. Additionally, it presented cytokines, whose concentration has a significant impact on the size of ovarian follicles, their number, the effectiveness of in vitro fertilisation, development of the embryo, and chances of correct implantation. Despite the many recent publications, the knowledge of follicular fluid immunology in the context of reproductive pathology is superficial and further research is required to extensively understand the roles of individual cytokines in reproductive pathology. In the future, this knowledge may enable patients’ individual qualifications to individual methods of infertility treatment, as well as the possible adjustment of the treatment regimen to the patient’s immune profile. Full article
18 pages, 2327 KiB  
Review
The Role of Chemokines in Cervical Cancers
by Fabian Garrido, Carl Mathis Wild, Johanna Mittelberger, Franziska Dobler, Mariella Schneider, Nadine Ansorge, Melitta Köpke, Annamarie Strieder, Nina Ditsch, Udo Jeschke and Christian Dannecker
Medicina 2021, 57(11), 1141; https://doi.org/10.3390/medicina57111141 - 21 Oct 2021
Cited by 11 | Viewed by 2962
Abstract
Both clinical-pathological and experimental studies have shown that chemokines play a key role in activating the immune checkpoint modulator in cervical cancer progression and are associated with prognosis in tumor cell proliferation, invasion, angiogenesis, chemoresistance, and immunosuppression. Therefore, a clear understanding of chemokines [...] Read more.
Both clinical-pathological and experimental studies have shown that chemokines play a key role in activating the immune checkpoint modulator in cervical cancer progression and are associated with prognosis in tumor cell proliferation, invasion, angiogenesis, chemoresistance, and immunosuppression. Therefore, a clear understanding of chemokines and immune checkpoint modulators is essential for the treatment of this disease. This review discusses the origins and categories of chemokines and the mechanisms that are responsible for activating immune checkpoints in cervical dysplasia and cancer, chemokines as biomarkers, and therapy development that targets immune checkpoints in cervical cancer research. Full article
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