Current Understanding on Why Ovarian Cancer Is Resistant to Immune Checkpoint Inhibitors
The standard treatment of ovarian cancer (OC) patients, including debulking surgery and first-line chemotherapy, is unsatisfactory because of recurrent episodes in the majority (~70%) of patients with advanced OC. Clinical trials have shown only a modest (10–15%) response of OC individuals to treatm...
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| Format: | Article |
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MDPI AG
2023-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/13/10859 |
| _version_ | 1797591573830041600 |
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| author | Anna Pawłowska Anna Rekowska Weronika Kuryło Anna Pańczyszyn Jan Kotarski Iwona Wertel |
| author_facet | Anna Pawłowska Anna Rekowska Weronika Kuryło Anna Pańczyszyn Jan Kotarski Iwona Wertel |
| author_sort | Anna Pawłowska |
| collection | DOAJ |
| description | The standard treatment of ovarian cancer (OC) patients, including debulking surgery and first-line chemotherapy, is unsatisfactory because of recurrent episodes in the majority (~70%) of patients with advanced OC. Clinical trials have shown only a modest (10–15%) response of OC individuals to treatment based on immune checkpoint inhibitors (ICIs). The resistance of OC to therapy is caused by various factors, including OC heterogeneity, low density of tumor-infiltrating lymphocytes (TILs), non-cellular and cellular interactions in the tumor microenvironment (TME), as well as a network of microRNA regulating immune checkpoint pathways. Moreover, ICIs are the most efficient in tumors that are marked by high microsatellite instability and high tumor mutation burden, which is rare among OC patients. The great challenge in ICI implementation is connected with distinguishing hyper-, pseudo-, and real progression of the disease. The understanding of the immunological, molecular, and genetic mechanisms of OC resistance is crucial to selecting the group of OC individuals in whom personalized treatment would be beneficial. In this review, we summarize current knowledge about the selected factors inducing OC resistance and discuss the future directions of ICI-based immunotherapy development for OC patients. |
| first_indexed | 2024-03-11T01:39:17Z |
| format | Article |
| id | doaj.art-aad52897614142e5a2f0228f614ec8b1 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T01:39:17Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-aad52897614142e5a2f0228f614ec8b12023-11-18T16:44:36ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-06-0124131085910.3390/ijms241310859Current Understanding on Why Ovarian Cancer Is Resistant to Immune Checkpoint InhibitorsAnna Pawłowska0Anna Rekowska1Weronika Kuryło2Anna Pańczyszyn3Jan Kotarski4Iwona Wertel5Independent Laboratory of Cancer Diagnostics and Immunology, Department of Oncological Gynaecology and Gynaecology, Faculty of Medicine, Medical University of Lublin, Chodźki 1, 20-093 Lublin, PolandStudents’ Scientific Association, Independent Laboratory of Cancer Diagnostics and Immunology, Medical University of Lublin, Chodźki 1, 20-093 Lublin, PolandStudents’ Scientific Association, Independent Laboratory of Cancer Diagnostics and Immunology, Medical University of Lublin, Chodźki 1, 20-093 Lublin, PolandInstitute of Medical Sciences, Department of Biology and Genetics, Faculty of Medicine, University of Opole, Oleska 48, 45-052 Opole, PolandIndependent Laboratory of Cancer Diagnostics and Immunology, Department of Oncological Gynaecology and Gynaecology, Faculty of Medicine, Medical University of Lublin, Chodźki 1, 20-093 Lublin, PolandIndependent Laboratory of Cancer Diagnostics and Immunology, Department of Oncological Gynaecology and Gynaecology, Faculty of Medicine, Medical University of Lublin, Chodźki 1, 20-093 Lublin, PolandThe standard treatment of ovarian cancer (OC) patients, including debulking surgery and first-line chemotherapy, is unsatisfactory because of recurrent episodes in the majority (~70%) of patients with advanced OC. Clinical trials have shown only a modest (10–15%) response of OC individuals to treatment based on immune checkpoint inhibitors (ICIs). The resistance of OC to therapy is caused by various factors, including OC heterogeneity, low density of tumor-infiltrating lymphocytes (TILs), non-cellular and cellular interactions in the tumor microenvironment (TME), as well as a network of microRNA regulating immune checkpoint pathways. Moreover, ICIs are the most efficient in tumors that are marked by high microsatellite instability and high tumor mutation burden, which is rare among OC patients. The great challenge in ICI implementation is connected with distinguishing hyper-, pseudo-, and real progression of the disease. The understanding of the immunological, molecular, and genetic mechanisms of OC resistance is crucial to selecting the group of OC individuals in whom personalized treatment would be beneficial. In this review, we summarize current knowledge about the selected factors inducing OC resistance and discuss the future directions of ICI-based immunotherapy development for OC patients.https://www.mdpi.com/1422-0067/24/13/10859ovarian cancerimmune checkpointsPD-1/PD-L1TIGITimmunotherapyresistance |
| spellingShingle | Anna Pawłowska Anna Rekowska Weronika Kuryło Anna Pańczyszyn Jan Kotarski Iwona Wertel Current Understanding on Why Ovarian Cancer Is Resistant to Immune Checkpoint Inhibitors International Journal of Molecular Sciences ovarian cancer immune checkpoints PD-1/PD-L1 TIGIT immunotherapy resistance |
| title | Current Understanding on Why Ovarian Cancer Is Resistant to Immune Checkpoint Inhibitors |
| title_full | Current Understanding on Why Ovarian Cancer Is Resistant to Immune Checkpoint Inhibitors |
| title_fullStr | Current Understanding on Why Ovarian Cancer Is Resistant to Immune Checkpoint Inhibitors |
| title_full_unstemmed | Current Understanding on Why Ovarian Cancer Is Resistant to Immune Checkpoint Inhibitors |
| title_short | Current Understanding on Why Ovarian Cancer Is Resistant to Immune Checkpoint Inhibitors |
| title_sort | current understanding on why ovarian cancer is resistant to immune checkpoint inhibitors |
| topic | ovarian cancer immune checkpoints PD-1/PD-L1 TIGIT immunotherapy resistance |
| url | https://www.mdpi.com/1422-0067/24/13/10859 |
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