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<p>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 (<i>p</i> = 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 (<i>p</i> = 0.004). In accordance, both treatments induced M-MDSCs (+ 5.34%) in MSS patients as compared to MSI-high patients (<i>p</i> = 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 (<i>p</i> = 0.020) and lower frequency of CD4+ (<i>p</i> &lt; 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.</p> Graphical abstract <p></p>

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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)

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月17日

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  • 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

摘要

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