Association of Peripheral Monocytic-Myeloid-Derived Suppressor Cells with Molecular Subtypes in Single Center Endometrial Cancer Patients Receiving Carboplatin + Paclitaxel/Avelumab (MITO END-3 Trial)

<p><span>The MITO-END3 trial compared carboplatin and paclitaxel (</span><span>CP</span><span>) with avelumab plus carboplatin and paclitaxel (</span><span>CPA)</span><span> as first-line treatment in endometrial cancer (EC) patients and </span><span>demonstrated a significant interaction between avelumab response and mismatch repair status. To investigate prognostic/predictive biomarker, </span><span>twenty-nine MITO-END3-EC patients were evaluated at pre-treatment (B1) and at the end of CP/CPA treatment (B2) for </span><span>peripheral Myeloid derived suppressor cells (MDSC) and Tregs. </span><span>At B2, <span>effector</span> 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, </span><span>primary tumors were highly infiltrated by M-MDSCs in MSS as compared to MSI-high ECs. </span><span>A post hoc analysis displayed higher frequeny of M-MDSCs (p=0.020) and lower frequency of CD4+ (p&lt;0.005) at pretreatment in EC patients as compared to healthy donors. </span><span>In conclusion, </span><span>the</span><span> 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. </span></p>