Predictive value of tumor microenvironment on pathologic response to neoadjuvant chemotherapy in patients with undifferentiated pleomorphic sarcomas

Undifferentiated pleomorphic sarcomas (UPS) represent a prevalent and aggressive subtype of soft tissue sarcomas (STS) in adults. Despite advancements in loco regional treatments, many patients with high grade STS, including UPS, develop metastatic disease. Neoadjuvant chemotherapy is a standard approach to mitigate this risk, but response variability necessitates refined patient selection strategies. This study investigated the correlation between UPS microenvironment and neoadjuvant chemotherapy response in resectable UPS. The NEOSARCOMICS study (NCT02789384) enrolled patients with resectable STS from six sarcoma centers in France. Patients received anthracycline based chemotherapy, followed by surgery. Histological response, gene expression profiling, and multiplex immunohistofluorescence were performed on baseline and post treatment tumor samples. Plasma proteomics was analyzed to identify biomarkers. Good responders to neoadjuvant chemotherapy showed enrichment in genes related to stemness and cell cycle regulation, while poor responders exhibited immune related gene enrichment. Proteomic profiling revealed immune pathway activation and downregulation of cell cycle pathways in non responders. Despite being associated with a good prognosis, high immune infiltration, particularly of CD8 + T cells and CD20 + B cells, predicts a poor response to neoadjuvant chemotherapy in UPS, suggesting the need for alternative therapeutic strategies for patients with inflamed UPS.Ongoing clinical trials are exploring the efficacy of combining chemotherapy with immune checkpoint inhibitors to improve outcomes.

• Publication year

  2024

• Venue

  Journal of Hematology & Oncology

• Publication date

  2024-10-23

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1186/s13045-024-01614-wPMID 39444039PMCID 11515614
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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