Predicting Response to Immunotargeted Therapy in Endometrial Cancer via Tumor Immune Microenvironment: A Multicenter, Observational Study
Only one-third of patients with advanced MSS/pMMR endometrial cancer exhibit a lasting response to the combination treatment of Pembrolizumab and Lenvatinib. The combined administration of these two drugs is based on Lenvatinib’s ability to modulate the tumor microenvironment, enabling Pembrolizumab...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/7/3933 |
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| author | Anastasia Maltseva Anna Kalinchuk Nataliya Chernorubashkina Virab Sisakyan Igor Lots Alina Gofman Yulia Anzhiganova Elizaveta Martynova Ruslan Zukov Elena Aleksandrova Larisa Kolomiets Liubov Tashireva |
| author_facet | Anastasia Maltseva Anna Kalinchuk Nataliya Chernorubashkina Virab Sisakyan Igor Lots Alina Gofman Yulia Anzhiganova Elizaveta Martynova Ruslan Zukov Elena Aleksandrova Larisa Kolomiets Liubov Tashireva |
| author_sort | Anastasia Maltseva |
| collection | DOAJ |
| description | Only one-third of patients with advanced MSS/pMMR endometrial cancer exhibit a lasting response to the combination treatment of Pembrolizumab and Lenvatinib. The combined administration of these two drugs is based on Lenvatinib’s ability to modulate the tumor microenvironment, enabling Pembrolizumab to exert its effect. These findings underscore the importance of exploring tumor microenvironment parameters to identify markers that can accurately select candidates for this type of therapy. An open non-randomized observational association study was conducted at six clinical centers, involving a total of 28 patients with advanced MSS/pMMR endometrial cancer who received Pembrolizumab and Lenvatinib therapy. Using TSA-associated multiplex immunofluorescence, we analyzed the proportion of CD8+ T lymphocytes, CD20+ B lymphocytes, FoxP3+ T regulatory lymphocytes, and CD163+ macrophages in tumor samples prior to immunotargeted therapy. The percentage of CD20+ B lymphocytes and the CD8-to-CD20 lymphocytes ratio was significantly higher in patients who responded to treatment compared to non-responders (responders vs. non-responders: 0.24 (0.1–1.24)% vs. 0.08 (0.00–0.15)%, <i>p</i> = 0.0114; 1.44 (0.58–2.70) arb. unit vs. 19.00 (3.80–34.78) arb. unit, <i>p</i> = 0.0031). The sensitivity and specificity of these biomarkers were 85.71% and 70.59%, and 85.71% and 85.71%, respectively. The proportion of CD20+ B lymphocytes and the CD8-to-CD20 lymphocytes ratio in the stroma of endometrial cancer serves as both a prognostic marker of response to immunotargeted therapy and a prognostic factor for progression-free survival in patients. |
| first_indexed | 2024-04-24T10:43:46Z |
| format | Article |
| id | doaj.art-cbe16023a7d449f68fd73d3da35d5b9f |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-04-24T10:43:46Z |
| publishDate | 2024-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-cbe16023a7d449f68fd73d3da35d5b9f2024-04-12T13:20:10ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-04-01257393310.3390/ijms25073933Predicting Response to Immunotargeted Therapy in Endometrial Cancer via Tumor Immune Microenvironment: A Multicenter, Observational StudyAnastasia Maltseva0Anna Kalinchuk1Nataliya Chernorubashkina2Virab Sisakyan3Igor Lots4Alina Gofman5Yulia Anzhiganova6Elizaveta Martynova7Ruslan Zukov8Elena Aleksandrova9Larisa Kolomiets10Liubov Tashireva11Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk 634050, RussiaCancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk 634050, RussiaIrkutsk Regional Oncology Center, 32 Frunze St., Irkutsk 664035, RussiaNovosibirsk Regional Clinical Oncology Center, 2 Plakhotnogo St., Novosibirsk 630108, RussiaNovosibirsk Regional Clinical Oncology Center, 2 Plakhotnogo St., Novosibirsk 630108, RussiaAltai Regional Oncological Dispensary, 110 Zmeinogorsky tr., Barnaul 656000, RussiaKrasnoyarsk Regional Clinical Oncological Dispensary Named after A. I. Kryzhanovsky, 16 1-ya Smolenskaya St., Krasnoyarsk 660133, RussiaKrasnoyarsk Regional Clinical Oncological Dispensary Named after A. I. Kryzhanovsky, 16 1-ya Smolenskaya St., Krasnoyarsk 660133, RussiaKrasnoyarsk Regional Clinical Oncological Dispensary Named after A. I. Kryzhanovsky, 16 1-ya Smolenskaya St., Krasnoyarsk 660133, RussiaYakut Republican Oncology Center, Build. 1, 81 Stadukhina St., Yakutsk 677005, RussiaCancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk 634050, RussiaCancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk 634050, RussiaOnly one-third of patients with advanced MSS/pMMR endometrial cancer exhibit a lasting response to the combination treatment of Pembrolizumab and Lenvatinib. The combined administration of these two drugs is based on Lenvatinib’s ability to modulate the tumor microenvironment, enabling Pembrolizumab to exert its effect. These findings underscore the importance of exploring tumor microenvironment parameters to identify markers that can accurately select candidates for this type of therapy. An open non-randomized observational association study was conducted at six clinical centers, involving a total of 28 patients with advanced MSS/pMMR endometrial cancer who received Pembrolizumab and Lenvatinib therapy. Using TSA-associated multiplex immunofluorescence, we analyzed the proportion of CD8+ T lymphocytes, CD20+ B lymphocytes, FoxP3+ T regulatory lymphocytes, and CD163+ macrophages in tumor samples prior to immunotargeted therapy. The percentage of CD20+ B lymphocytes and the CD8-to-CD20 lymphocytes ratio was significantly higher in patients who responded to treatment compared to non-responders (responders vs. non-responders: 0.24 (0.1–1.24)% vs. 0.08 (0.00–0.15)%, <i>p</i> = 0.0114; 1.44 (0.58–2.70) arb. unit vs. 19.00 (3.80–34.78) arb. unit, <i>p</i> = 0.0031). The sensitivity and specificity of these biomarkers were 85.71% and 70.59%, and 85.71% and 85.71%, respectively. The proportion of CD20+ B lymphocytes and the CD8-to-CD20 lymphocytes ratio in the stroma of endometrial cancer serves as both a prognostic marker of response to immunotargeted therapy and a prognostic factor for progression-free survival in patients.https://www.mdpi.com/1422-0067/25/7/3933endometrial cancerimmunotargeted therapytumor microenvironmentlymphocytes |
| spellingShingle | Anastasia Maltseva Anna Kalinchuk Nataliya Chernorubashkina Virab Sisakyan Igor Lots Alina Gofman Yulia Anzhiganova Elizaveta Martynova Ruslan Zukov Elena Aleksandrova Larisa Kolomiets Liubov Tashireva Predicting Response to Immunotargeted Therapy in Endometrial Cancer via Tumor Immune Microenvironment: A Multicenter, Observational Study International Journal of Molecular Sciences endometrial cancer immunotargeted therapy tumor microenvironment lymphocytes |
| title | Predicting Response to Immunotargeted Therapy in Endometrial Cancer via Tumor Immune Microenvironment: A Multicenter, Observational Study |
| title_full | Predicting Response to Immunotargeted Therapy in Endometrial Cancer via Tumor Immune Microenvironment: A Multicenter, Observational Study |
| title_fullStr | Predicting Response to Immunotargeted Therapy in Endometrial Cancer via Tumor Immune Microenvironment: A Multicenter, Observational Study |
| title_full_unstemmed | Predicting Response to Immunotargeted Therapy in Endometrial Cancer via Tumor Immune Microenvironment: A Multicenter, Observational Study |
| title_short | Predicting Response to Immunotargeted Therapy in Endometrial Cancer via Tumor Immune Microenvironment: A Multicenter, Observational Study |
| title_sort | predicting response to immunotargeted therapy in endometrial cancer via tumor immune microenvironment a multicenter observational study |
| topic | endometrial cancer immunotargeted therapy tumor microenvironment lymphocytes |
| url | https://www.mdpi.com/1422-0067/25/7/3933 |
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