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Immunologic correlates in a CIC::DUX4 fusion-positive sarcoma responsive to dual immune checkpoint blockade
Olayode O Babatunde1, Sara Coca Membribes2, Cristina Anthonescu3
1Medical Oncology/Hematology Fellowship Program, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. babatuo@mskcc.org.
Abstract:
CIC::DUX4 sarcoma (CDS) is a rare and aggressive subtype of soft tissue sarcoma with poor prognosis and limited treatment options. Immunotherapy has not been studied in this disease. To our knowledge, response to immune checkpoint blockade (ICB) has not been previously reported. Here, we present the first case of a patient with CDS responding to dual ICB with nivolumab and relatlimab. Immunohistochemical (IHC) analysis of pre-treatment samples revealed minimal immune cell infiltration, with scarce CD3+, CD8+, and FOXP3+ T-cells and negligible expression of PD-L1 and PD-1 markers. Post-treatment tumor samples revealed a significant shift in the immune microenvironment, with increased CD8 + T-cell infiltration and co-expression of exhaustion markers PD-1 and LAG-3 following treatment. These findings suggest that doublet ICB can activate an antitumor immune response in CDS, overcoming the immune cold phenotype typically associated with this sarcoma. This case provides the first evidence of dual PD-1/LAG-3 blockade inducing an immune response in CDS. The favorable response and tolerability observed in this patient highlight the potential of dual ICB as a therapeutic option in CDS that merits further investigation.
Insights
This study reports the first case of CIC::DUX4 sarcoma (CDS) responding to dual immune checkpoint blockade (ICB) therapy. The treatment activated an antitumor immune response, suggesting potential for CDS immunotherapy.
Area of Science:
- Oncology
- Immunology
- Sarcoma Research
Background:
- CIC::DUX4 sarcoma (CDS) is an aggressive soft tissue sarcoma with limited treatment options and poor prognosis.
- Immunotherapy, specifically immune checkpoint blockade (ICB), has not been previously investigated in CDS.
- The immune microenvironment of CDS is typically characterized as 'immune cold' with minimal immune cell infiltration.
Purpose of the Study:
- To report the first case of a patient with CDS responding to dual ICB therapy.
- To investigate the impact of dual ICB on the tumor immune microenvironment in CDS.
- To assess the potential of dual ICB as a therapeutic strategy for CDS.
Main Methods:
- A single patient with CDS received dual ICB with nivolumab and relatlimab.
- Immunohistochemical (IHC) analysis was performed on pre-treatment and post-treatment tumor samples.
- Analysis focused on immune cell infiltration (CD3+, CD8+, FOXP3+) and immune checkpoint marker expression (PD-L1, PD-1, LAG-3).
Main Results:
- The patient showed a response to dual ICB therapy.
- Pre-treatment samples showed minimal immune infiltration and low PD-L1/PD-1 expression.
- Post-treatment samples revealed increased CD8+ T-cell infiltration and co-expression of PD-1 and LAG-3, indicating an activated immune response.
Conclusions:
- Dual ICB with nivolumab and relatlimab can induce an antitumor immune response in CDS.
- This therapy may overcome the immune-cold phenotype characteristic of CDS.
- Dual ICB shows potential as a tolerable and effective therapeutic option for CDS, warranting further investigation.
