Peripheral Monocytic-Myeloid-Derived Suppressor Cells contribute in identifying endometrial cancer patients responder to Carboplatin + Paclitaxel/Avelumab in advanced or recurrent endometrial cancer (MITO END-3 trial)

Purpose: The MITO-END3 trial compared carboplatin and paclitaxel (CP) versus avelumab plus carboplatin and paclitaxel (CPA) as first-line treatment in endometrial cancer (EC) patients and demonstrated a significant interaction between treatment and mismatch repair status. EC-tumor microenvironment (TME) is infiltrated of myeloid and T-regulatory cells that limit response to therapy. To investigate on potential predictive biomarkers, myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg) were evaluated in peripheral blood of a subcohort of MITO END-3 patients. Experimental design: Peripheral blood was collected from 29 EC patients at pre-treatment (B1) and at the end of CP/CPA treatment (B2). MDSC were evaluated as monocytic (M-MDSC), early-stage (E-MDSC), polymorphonuclear (PMN-MDSC), and Tregs. For 27 EC patients both B1 and B2 samples were available and 23 out of 27 matched-pairs patients with complete Cancer Genome Atlas (TCGA) and microsatellite instability (MSI) molecular data. Results: At the end of 6 cycles of therapy (B2), Tregs was significantly higher in avelumab combination compared to chemotherapy-alone (p=0.038). Treatments (CP/CPA) induced significant decrease in M-MDSC (-5.41%) (p=0.004) in TCGA 2-MSI-High as compared to TCGA-category 4 tumors. In accordance, treatments induced M-MDSCs (+ 5.34%) in MSI-Stable patients as compared to MSI-High patients (p=0.001). Finally, a post hoc analysis showed at baseline higher levels of M-MDSCs (p=0.020) and lower levels of CD4+ (p<0.005) compared to healthy donors Conclusions: M-MDSC peripheral monitoring may add insights in identifying EC patients responder to first line chemo/chemo-immunotherapy.