Association of peripheral monocytic myeloid-derived suppressor cells with molecular subtypes in single-center endometrial cancer patients receiving carboplatin + paclitaxel/avelumab (MITO-END3 trial)
Abstract The MITO-END3 trial compared carboplatin and paclitaxel (CP) with avelumab plus carboplatin and paclitaxel (CPA) as first-line treatment in endometrial cancer (EC) patients and demonstrated a significant interaction between avelumab response and mismatch repair status. To investigate progno...
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| Language: | English |
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Springer
2025-04-01
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| Series: | Cancer Immunology, Immunotherapy |
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| Online Access: | https://doi.org/10.1007/s00262-025-04021-3 |
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| author | C. D’Alterio G. Rea M. Napolitano E. Coppola A. Spina D. Russo R. Azzaro C. Mignogna G. Scognamiglio D. Califano L. Arenare C. Schettino C. Pisano S. C. Cecere M. Di Napoli A. Passarelli F. Perrone S. Pignata S. Scala |
| author_facet | C. D’Alterio G. Rea M. Napolitano E. Coppola A. Spina D. Russo R. Azzaro C. Mignogna G. Scognamiglio D. Califano L. Arenare C. Schettino C. Pisano S. C. Cecere M. Di Napoli A. Passarelli F. Perrone S. Pignata S. Scala |
| author_sort | C. D’Alterio |
| collection | DOAJ |
| description | Abstract The MITO-END3 trial compared carboplatin and paclitaxel (CP) with avelumab plus carboplatin and paclitaxel (CPA) as first-line treatment in endometrial cancer (EC) patients and demonstrated a significant interaction between avelumab response and mismatch repair status. To investigate prognostic/predictive biomarker, 29 MITO-END3-EC patients were evaluated at pretreatment (B1) and at the end of CP/CPA treatment (B2) for peripheral myeloid-derived suppressor cells (MDSC) and Tregs. At B2, effector Tregs frequency was significantly higher in patients treated with CPA as compared to CP (p = 0.038). Both treatments (CP/CPA) induced significant decrease in peripheral M-MDSC (− 5.41%) in TCGA 2-MSI-high as compared to TCGA-category 4 tumors (p = 0.004). In accordance, both treatments induced M-MDSCs (+ 5.34%) in MSS patients as compared to MSI-high patients (p = 0.001). Moreover, in a subgroup of patients, primary tumors were highly infiltrated by M-MDSCs in MSS as compared to MSI-high ECs. A post hoc analysis displayed higher frequency of M-MDSCs (p = 0.020) and lower frequency of CD4+ (p < 0.005) at pretreatment in EC patients as compared to healthy donors. In conclusion, the peripheral evaluation of MDSCs and Tregs correlated with molecular features in EC treated with CP/CPA and may add insights in identifying EC patients responder to first-line chemo/chemo-immunotherapy. Graphical abstract |
| format | Article |
| id | doaj-art-c6fb3dbc144e476d865bba6faa37e426 |
| institution | DOAJ |
| issn | 1432-0851 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Springer |
| record_format | Article |
| series | Cancer Immunology, Immunotherapy |
| spelling | doaj-art-c6fb3dbc144e476d865bba6faa37e4262025-08-20T03:08:25ZengSpringerCancer Immunology, Immunotherapy1432-08512025-04-0174611210.1007/s00262-025-04021-3Association of peripheral monocytic myeloid-derived suppressor cells with molecular subtypes in single-center endometrial cancer patients receiving carboplatin + paclitaxel/avelumab (MITO-END3 trial)C. D’Alterio0G. Rea1M. Napolitano2E. Coppola3A. Spina4D. Russo5R. Azzaro6C. Mignogna7G. Scognamiglio8D. Califano9L. Arenare10C. Schettino11C. Pisano12S. C. Cecere13M. Di Napoli14A. Passarelli15F. Perrone16S. Pignata17S. Scala18Microenvironment Molecular Targets, Istituto Nazionale per lo Studio e la Cura dei Tumori-IRCCS-Fondazione “G. Pascale”Microenvironment Molecular Targets, Istituto Nazionale per lo Studio e la Cura dei Tumori-IRCCS-Fondazione “G. Pascale”Microenvironment Molecular Targets, Istituto Nazionale per lo Studio e la Cura dei Tumori-IRCCS-Fondazione “G. Pascale”Uro-Gynecology Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori-IRCCS-Fondazione “G. Pascale”Microenvironment Molecular Targets, Istituto Nazionale per lo Studio e la Cura dei Tumori-IRCCS-Fondazione “G. Pascale”Microenvironment Molecular Targets, Istituto Nazionale per lo Studio e la Cura dei Tumori-IRCCS-Fondazione “G. Pascale”Transfusion Medicine Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori-IRCCS-Fondazione “G. Pascale”Pathology, Istituto Nazionale per lo Studio e la Cura dei Tumori-IRCCS-Fondazione “G. Pascale”Pathology, Istituto Nazionale per lo Studio e la Cura dei Tumori-IRCCS-Fondazione “G. Pascale”Microenvironment Molecular Targets, Istituto Nazionale per lo Studio e la Cura dei Tumori-IRCCS-Fondazione “G. Pascale”Clinical Trial Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori-IRCCS-Fondazione “G. Pascale”Clinical Trial Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori-IRCCS-Fondazione “G. Pascale”Uro-Gynecology Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori-IRCCS-Fondazione “G. Pascale”Uro-Gynecology Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori-IRCCS-Fondazione “G. Pascale”Uro-Gynecology Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori-IRCCS-Fondazione “G. Pascale”Uro-Gynecology Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori-IRCCS-Fondazione “G. Pascale”Clinical Trial Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori-IRCCS-Fondazione “G. Pascale”Uro-Gynecology Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori-IRCCS-Fondazione “G. Pascale”Microenvironment Molecular Targets, Istituto Nazionale per lo Studio e la Cura dei Tumori-IRCCS-Fondazione “G. Pascale”Abstract The MITO-END3 trial compared carboplatin and paclitaxel (CP) with avelumab plus carboplatin and paclitaxel (CPA) as first-line treatment in endometrial cancer (EC) patients and demonstrated a significant interaction between avelumab response and mismatch repair status. To investigate prognostic/predictive biomarker, 29 MITO-END3-EC patients were evaluated at pretreatment (B1) and at the end of CP/CPA treatment (B2) for peripheral myeloid-derived suppressor cells (MDSC) and Tregs. At B2, effector Tregs frequency was significantly higher in patients treated with CPA as compared to CP (p = 0.038). Both treatments (CP/CPA) induced significant decrease in peripheral M-MDSC (− 5.41%) in TCGA 2-MSI-high as compared to TCGA-category 4 tumors (p = 0.004). In accordance, both treatments induced M-MDSCs (+ 5.34%) in MSS patients as compared to MSI-high patients (p = 0.001). Moreover, in a subgroup of patients, primary tumors were highly infiltrated by M-MDSCs in MSS as compared to MSI-high ECs. A post hoc analysis displayed higher frequency of M-MDSCs (p = 0.020) and lower frequency of CD4+ (p < 0.005) at pretreatment in EC patients as compared to healthy donors. In conclusion, the peripheral evaluation of MDSCs and Tregs correlated with molecular features in EC treated with CP/CPA and may add insights in identifying EC patients responder to first-line chemo/chemo-immunotherapy. Graphical abstracthttps://doi.org/10.1007/s00262-025-04021-3Endometrial cancerChemotherapyAvelumabMyeloid-derived suppressor cellsThe Cancer Genome Atlas (TCGA)-based molecular classification |
| spellingShingle | C. D’Alterio G. Rea M. Napolitano E. Coppola A. Spina D. Russo R. Azzaro C. Mignogna G. Scognamiglio D. Califano L. Arenare C. Schettino C. Pisano S. C. Cecere M. Di Napoli A. Passarelli F. Perrone S. Pignata S. Scala Association of peripheral monocytic myeloid-derived suppressor cells with molecular subtypes in single-center endometrial cancer patients receiving carboplatin + paclitaxel/avelumab (MITO-END3 trial) Cancer Immunology, Immunotherapy Endometrial cancer Chemotherapy Avelumab Myeloid-derived suppressor cells The Cancer Genome Atlas (TCGA)-based molecular classification |
| title | Association of peripheral monocytic myeloid-derived suppressor cells with molecular subtypes in single-center endometrial cancer patients receiving carboplatin + paclitaxel/avelumab (MITO-END3 trial) |
| title_full | Association of peripheral monocytic myeloid-derived suppressor cells with molecular subtypes in single-center endometrial cancer patients receiving carboplatin + paclitaxel/avelumab (MITO-END3 trial) |
| title_fullStr | Association of peripheral monocytic myeloid-derived suppressor cells with molecular subtypes in single-center endometrial cancer patients receiving carboplatin + paclitaxel/avelumab (MITO-END3 trial) |
| title_full_unstemmed | Association of peripheral monocytic myeloid-derived suppressor cells with molecular subtypes in single-center endometrial cancer patients receiving carboplatin + paclitaxel/avelumab (MITO-END3 trial) |
| title_short | Association of peripheral monocytic myeloid-derived suppressor cells with molecular subtypes in single-center endometrial cancer patients receiving carboplatin + paclitaxel/avelumab (MITO-END3 trial) |
| title_sort | association of peripheral monocytic myeloid derived suppressor cells with molecular subtypes in single center endometrial cancer patients receiving carboplatin paclitaxel avelumab mito end3 trial |
| topic | Endometrial cancer Chemotherapy Avelumab Myeloid-derived suppressor cells The Cancer Genome Atlas (TCGA)-based molecular classification |
| url | https://doi.org/10.1007/s00262-025-04021-3 |
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