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Association of peripheral monocytic myeloid-derived suppressor cells with molecular subtypes in single-center endometrial cancer patients receiving carboplatin + paclitaxel/avelumab (MITO-END3 trial)
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Association of peripheral monocytic myeloid-derived suppressor cells with molecular subtypes in single-center endometrial cancer patients receiving carboplatin + paclitaxel/avelumab (MITO-END3 trial)
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Association of peripheral monocytic myeloid-derived suppressor cells with molecular subtypes in single-center endometrial cancer patients receiving carboplatin + paclitaxel/avelumab (MITO-END3 trial)
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Journal Article
Association of peripheral monocytic myeloid-derived suppressor cells with molecular subtypes in single-center endometrial cancer patients receiving carboplatin + paclitaxel/avelumab (MITO-END3 trial)
2025
Overview
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
Publisher
Springer Berlin Heidelberg,Springer Nature B.V,Springer
Subject
/ Aged
/ Antibodies, Monoclonal, Humanized - administration & dosage
/ Antineoplastic Combined Chemotherapy Protocols - therapeutic use
/ Avelumab
/ Carboplatin - administration & dosage
/ Carboplatin - therapeutic use
/ Endometrial Neoplasms - drug therapy
/ Endometrial Neoplasms - immunology
/ Endometrial Neoplasms - pathology
/ Female
/ Humans
/ Medicine
/ Myeloid-derived suppressor cells
/ Myeloid-Derived Suppressor Cells - immunology
/ Myeloid-Derived Suppressor Cells - metabolism
/ Oncology
/ Paclitaxel - administration & dosage
/ Paclitaxel - therapeutic use
/ T-Lymphocytes, Regulatory - immunology
/ The Cancer Genome Atlas (TCGA)-based molecular classification
/ Tumors
