TIGIT immunosuppressive role in female reproductive system malignant neoplasms: from mechanism to therapy
Introduction. Malignant neoplasms of the female reproductive system (ovarian, endometrial, and cervical cancers) account for a significant proportion of female oncology morbidity and mortality. Standard treatment methods, including surgery, chemotherapy, and radiotherapy, show limited efficacy in re...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | Russian |
| Published: |
IRBIS LLC
2020-04-01
|
| Series: | Акушерство, гинекология и репродукция |
| Subjects: | |
| Online Access: | https://www.gynecology.su/jour/article/view/2483 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1839583413267333120 |
|---|---|
| author | A. U. Khamadyanova A. I. Romanova A. N. Sklyar A. P. Yamilova M. G. Miranda Planas G. D. Galeeva S. R. Khakimov A. A. Yakubov S. K. Bikinyaev Sh. M. Mammaev A. A. Vardanyan P. A. Kantaeva T. R. Algirieva |
| author_facet | A. U. Khamadyanova A. I. Romanova A. N. Sklyar A. P. Yamilova M. G. Miranda Planas G. D. Galeeva S. R. Khakimov A. A. Yakubov S. K. Bikinyaev Sh. M. Mammaev A. A. Vardanyan P. A. Kantaeva T. R. Algirieva |
| author_sort | A. U. Khamadyanova |
| collection | DOAJ |
| description | Introduction. Malignant neoplasms of the female reproductive system (ovarian, endometrial, and cervical cancers) account for a significant proportion of female oncology morbidity and mortality. Standard treatment methods, including surgery, chemotherapy, and radiotherapy, show limited efficacy in recurrent and drug-resistant tumors. The development of immunotherapy, particularly immune checkpoint inhibitors (ICI), has opened new therapeutic avenues; however, their clinical effectiveness in gynecologic oncology remains suboptimal. In connection with this, it has increased an interest in novel targets, notably TIGIT (T-cell immunoglobulin and ITIM domain), a co-inhibitory receptor expressed on T-cells and natural killer cells (NK-cells), which plays a key role in establishing an immunosuppressive tumor microenvironment.Aim: to systematize current data on the biological function of TIGIT and relevant ligands, its role in immunosuppression in malignant neoplasms of the female reproductive system as well as evaluate a therapeutic potential of its blockade during a personalized immunotherapy.Materials and Methods. This review was conducted according to the PRISMA methodology. There was performed a systematic literature search for publications from 2013 to 2024 in the databases PubMed/MEDLINE, Scopus, Web of Science, Embase, Google Scholar, and ClinicalTrials.gov. A total of 91 scientific sources and 7 registered clinical trials were included. Original studies, meta-analyses, reviews, guidelines, and clinical trial reports were analyzed.Results. TIGIT interacts with several ligands (CD155, CD112, Nectin-4, Fap2), leading to suppression of NK-cells and CD8+ T-cells activity, macrophage polarization toward M2 phenotype, activation of regulatory T-cells (Treg), and impaired antigen presentation. TIGIT is co-expressed with PD-1 (programmed cell death protein 1) and CD96, forming a suppressive signaling network. Its elevated expression is associated with disease progression in ovarian, endometrial, and cervical cancers, reduced cytotoxicity of tumor-infiltrating lymphocytes (TIL), and poor prognosis. TIGIT blockade, especially in combination with PD-1/PD-L1 (programmed cell death ligand 1), restores effector cell function and enhances antitumor immunity in preclinical and clinical studies.Conclusion. TIGIT is a promising immunotherapeutic target in malignant neoplasms of the female reproductive system. Its blockade may improve treatment outcomes in patients with recurrent and resistant cancert ypes. Combined approaches involving anti-TIGIT agents require further clinical validation but even today they offer new directions in targeted therapy and personalized management in gynecologic oncology. |
| format | Article |
| id | doaj-art-db2a82ce73c84a529616c7fb038077b7 |
| institution | Matheson Library |
| issn | 2313-7347 2500-3194 |
| language | Russian |
| publishDate | 2020-04-01 |
| publisher | IRBIS LLC |
| record_format | Article |
| series | Акушерство, гинекология и репродукция |
| spelling | doaj-art-db2a82ce73c84a529616c7fb038077b72025-08-03T19:55:19ZrusIRBIS LLCАкушерство, гинекология и репродукция2313-73472500-31942020-04-010010.17749/2313-7347/ob.gyn.rep.2025.647982TIGIT immunosuppressive role in female reproductive system malignant neoplasms: from mechanism to therapyA. U. Khamadyanova0A. I. Romanova1A. N. Sklyar2A. P. Yamilova3M. G. Miranda Planas4G. D. Galeeva5S. R. Khakimov6A. A. Yakubov7S. K. Bikinyaev8Sh. M. Mammaev9A. A. Vardanyan10P. A. Kantaeva11T. R. Algirieva12Bashkir State Medical University, Ministry of Health of the Russian FederationRussian University of Medicine, Ministry of Health of the Russian FederationIvanovo State Medical University, Ministry of Health of the Russian FederationUral State Medical University, Ministry of Health of the Russian FederationPrimary Health Care Center No. 3Bashkir State Medical University, Ministry of Health of the Russian FederationBashkir State Medical University, Ministry of Health of the Russian FederationAvicenna Tajik State Medical UniversityRegional Clinical Hospital No. 2Rostov State Medical University, Ministry of Health of the Russian FederationRostov State Medical University, Ministry of Health of the Russian FederationKadyrov Chechen State UniversityPatrice Lumumba Peoples' Friendship University of RussiaIntroduction. Malignant neoplasms of the female reproductive system (ovarian, endometrial, and cervical cancers) account for a significant proportion of female oncology morbidity and mortality. Standard treatment methods, including surgery, chemotherapy, and radiotherapy, show limited efficacy in recurrent and drug-resistant tumors. The development of immunotherapy, particularly immune checkpoint inhibitors (ICI), has opened new therapeutic avenues; however, their clinical effectiveness in gynecologic oncology remains suboptimal. In connection with this, it has increased an interest in novel targets, notably TIGIT (T-cell immunoglobulin and ITIM domain), a co-inhibitory receptor expressed on T-cells and natural killer cells (NK-cells), which plays a key role in establishing an immunosuppressive tumor microenvironment.Aim: to systematize current data on the biological function of TIGIT and relevant ligands, its role in immunosuppression in malignant neoplasms of the female reproductive system as well as evaluate a therapeutic potential of its blockade during a personalized immunotherapy.Materials and Methods. This review was conducted according to the PRISMA methodology. There was performed a systematic literature search for publications from 2013 to 2024 in the databases PubMed/MEDLINE, Scopus, Web of Science, Embase, Google Scholar, and ClinicalTrials.gov. A total of 91 scientific sources and 7 registered clinical trials were included. Original studies, meta-analyses, reviews, guidelines, and clinical trial reports were analyzed.Results. TIGIT interacts with several ligands (CD155, CD112, Nectin-4, Fap2), leading to suppression of NK-cells and CD8+ T-cells activity, macrophage polarization toward M2 phenotype, activation of regulatory T-cells (Treg), and impaired antigen presentation. TIGIT is co-expressed with PD-1 (programmed cell death protein 1) and CD96, forming a suppressive signaling network. Its elevated expression is associated with disease progression in ovarian, endometrial, and cervical cancers, reduced cytotoxicity of tumor-infiltrating lymphocytes (TIL), and poor prognosis. TIGIT blockade, especially in combination with PD-1/PD-L1 (programmed cell death ligand 1), restores effector cell function and enhances antitumor immunity in preclinical and clinical studies.Conclusion. TIGIT is a promising immunotherapeutic target in malignant neoplasms of the female reproductive system. Its blockade may improve treatment outcomes in patients with recurrent and resistant cancert ypes. Combined approaches involving anti-TIGIT agents require further clinical validation but even today they offer new directions in targeted therapy and personalized management in gynecologic oncology.https://www.gynecology.su/jour/article/view/2483t-cell immunoglobulin and itim domaintigitimmunotherapyimmune checkpointsgynecologic malignanciesovarian cancerendometrial cancercervical cancer |
| spellingShingle | A. U. Khamadyanova A. I. Romanova A. N. Sklyar A. P. Yamilova M. G. Miranda Planas G. D. Galeeva S. R. Khakimov A. A. Yakubov S. K. Bikinyaev Sh. M. Mammaev A. A. Vardanyan P. A. Kantaeva T. R. Algirieva TIGIT immunosuppressive role in female reproductive system malignant neoplasms: from mechanism to therapy Акушерство, гинекология и репродукция t-cell immunoglobulin and itim domain tigit immunotherapy immune checkpoints gynecologic malignancies ovarian cancer endometrial cancer cervical cancer |
| title | TIGIT immunosuppressive role in female reproductive system malignant neoplasms: from mechanism to therapy |
| title_full | TIGIT immunosuppressive role in female reproductive system malignant neoplasms: from mechanism to therapy |
| title_fullStr | TIGIT immunosuppressive role in female reproductive system malignant neoplasms: from mechanism to therapy |
| title_full_unstemmed | TIGIT immunosuppressive role in female reproductive system malignant neoplasms: from mechanism to therapy |
| title_short | TIGIT immunosuppressive role in female reproductive system malignant neoplasms: from mechanism to therapy |
| title_sort | tigit immunosuppressive role in female reproductive system malignant neoplasms from mechanism to therapy |
| topic | t-cell immunoglobulin and itim domain tigit immunotherapy immune checkpoints gynecologic malignancies ovarian cancer endometrial cancer cervical cancer |
| url | https://www.gynecology.su/jour/article/view/2483 |
| work_keys_str_mv | AT aukhamadyanova tigitimmunosuppressiveroleinfemalereproductivesystemmalignantneoplasmsfrommechanismtotherapy AT airomanova tigitimmunosuppressiveroleinfemalereproductivesystemmalignantneoplasmsfrommechanismtotherapy AT ansklyar tigitimmunosuppressiveroleinfemalereproductivesystemmalignantneoplasmsfrommechanismtotherapy AT apyamilova tigitimmunosuppressiveroleinfemalereproductivesystemmalignantneoplasmsfrommechanismtotherapy AT mgmirandaplanas tigitimmunosuppressiveroleinfemalereproductivesystemmalignantneoplasmsfrommechanismtotherapy AT gdgaleeva tigitimmunosuppressiveroleinfemalereproductivesystemmalignantneoplasmsfrommechanismtotherapy AT srkhakimov tigitimmunosuppressiveroleinfemalereproductivesystemmalignantneoplasmsfrommechanismtotherapy AT aayakubov tigitimmunosuppressiveroleinfemalereproductivesystemmalignantneoplasmsfrommechanismtotherapy AT skbikinyaev tigitimmunosuppressiveroleinfemalereproductivesystemmalignantneoplasmsfrommechanismtotherapy AT shmmammaev tigitimmunosuppressiveroleinfemalereproductivesystemmalignantneoplasmsfrommechanismtotherapy AT aavardanyan tigitimmunosuppressiveroleinfemalereproductivesystemmalignantneoplasmsfrommechanismtotherapy AT pakantaeva tigitimmunosuppressiveroleinfemalereproductivesystemmalignantneoplasmsfrommechanismtotherapy AT tralgirieva tigitimmunosuppressiveroleinfemalereproductivesystemmalignantneoplasmsfrommechanismtotherapy |