Faculty, Staff and Student Publications

Language

English

Publication Date

4-1-2024

Journal

Nature Cancer

DOI

10.1038/s43018-024-00726-z

PMID

38351182

PMCID

PMC12955605

PubMedCentral® Posted Date

3-4-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

Based on the demonstrated clinical activity of immune-checkpoint blockade (ICB) in advanced dedifferentiated liposarcoma (DDLPS) and undifferentiated pleomorphic sarcoma (UPS), we conducted a randomized, non-comparative phase 2 trial ( NCT03307616 ) of neoadjuvant nivolumab or nivolumab/ipilimumab in patients with resectable retroperitoneal DDLPS (n = 17) and extremity/truncal UPS (+ concurrent nivolumab/radiation therapy; n = 10). The primary end point of pathologic response (percent hyalinization) was a median of 8.8% in DDLPS and 89% in UPS. Secondary end points were the changes in immune infiltrate, radiographic response, 12- and 24-month relapse-free survival and overall survival. Lower densities of regulatory T cells before treatment were associated with a major pathologic response (hyalinization > 30%). Tumor infiltration by B cells was increased following neoadjuvant treatment and was associated with overall survival in DDLPS. B cell infiltration was associated with higher densities of regulatory T cells before treatment, which was lost upon ICB treatment. Our data demonstrate that neoadjuvant ICB is associated with complex immune changes within the tumor microenvironment in DDLPS and UPS and that neoadjuvant ICB with concurrent radiotherapy has significant efficacy in UPS.

Keywords

Humans, Liposarcoma, Neoadjuvant Therapy, Retroperitoneal Neoplasms, Male, Female, Immune Checkpoint Inhibitors, Middle Aged, Aged, T-Lymphocytes, Regulatory, Adult, Sarcoma, Nivolumab, B-Lymphocytes

Published Open-Access

yes

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